Caspase 3: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Caspase 9: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.Caspase 8: A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.Caspase 7: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Caspases: A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.Caspase 1: A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.Caspase 10: A long pro-domain caspase that contains a death effector domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS. Caspase 10 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Amino Acid Chloromethyl Ketones: Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Caspase 12: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 12 is activated by pro-apoptotic factors that are released during cell stress and by CARD SIGNALING ADAPTOR PROTEINS. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.Caspase 14: A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.DNA Fragmentation: Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.Proto-Oncogene Proteins c-bcl-2: Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.Cytochromes c: Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Antigens, CD95: A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Cytochrome c Group: A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)X-Linked Inhibitor of Apoptosis Protein: An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.Poly(ADP-ribose) Polymerases: Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.Apoptotic Protease-Activating Factor 1: A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.bcl-2-Associated X Protein: A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Inhibitor of Apoptosis Proteins: A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Caspases, Initiator: A subtype of caspases that contain long pro-domain regions that regulate the activation of the enzyme. The pro-domain regions contain protein-protein interaction motifs that can interact with specific signaling adaptor proteins such as DEATH DOMAIN RECEPTORS; DED SIGNALING ADAPTOR PROTEINS; and CARD SIGNALING ADAPTOR PROTEINS. Once activated, the initiator caspases can activate other caspases such as the EFFECTOR CASPASES.In Situ Nick-End Labeling: An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.BH3 Interacting Domain Death Agonist Protein: A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.Apoptosis Regulatory Proteins: A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Cell Line, Tumor: A cell line derived from cultured tumor cells.Cysteine Endopeptidases: ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.Oligopeptides: Peptides composed of between two and twelve amino acids.Fas-Associated Death Domain Protein: A signal-transducing adaptor protein that associates with TNF RECEPTOR complexes. It contains a death effector domain that can interact with death effector domains found on INITIATOR CASPASES such as CASPASE 8 and CASPASE 10. Activation of CASPASES via interaction with this protein plays a role in the signaling cascade that leads to APOPTOSIS.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cell Line: Established cell cultures that have the potential to propagate indefinitely.bcl-X Protein: A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.Apoptosis Inducing Factor: A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.CASP8 and FADD-Like Apoptosis Regulating Protein: An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.Staurosporine: An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)Annexin A5: A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.Membrane Potential, Mitochondrial: The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.HL-60 Cells: A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)TNF-Related Apoptosis-Inducing Ligand: A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Necrosis: The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.Caspases, Effector: A subclass of caspases that contain short pro-domain regions. They are activated by the proteolytic action of INITIATOR CASPASES. Once activated they cleave a variety of substrates that cause APOPTOSIS.Apoptosomes: Multimeric protein complexes formed in the CYTOSOL that play a role in the activation of APOPTOSIS. They can occur when MITOCHONDRIA become damaged due to cell stress and release CYTOCHROME C. Cytosolic cytochrome C associates with APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 to form the apoptosomal protein complex. The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.CRADD Signaling Adaptor Protein: A death domain receptor signaling adaptor protein that plays a role in signaling the activation of INITIATOR CASPASES such as CASPASE 2. It contains a death domain that is specific for RIP SERINE-THEONINE KINASES and a caspase-binding domain that binds to and activates CASPASES such as CASPASE 2.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Death Domain Receptor Signaling Adaptor Proteins: Intracellular signaling adaptor proteins that bind to the cytoplasmic death domain region found on DEATH DOMAIN RECEPTORS. Many of the proteins in this class take part in intracellular signaling from TUMOR NECROSIS FACTOR RECEPTORS.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Phosphatidylserines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.CARD Signaling Adaptor Proteins: A family of intracellular signaling adaptor proteins that contain caspase activation and recruitment domains. Proteins that contain this domain play a role in APOPTOSIS-related signal transduction by associating with other CARD domain-containing members and in activating INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.bcl-2 Homologous Antagonist-Killer Protein: A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 184.108.40.206.Granzymes: A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Mitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Receptor-Interacting Protein Serine-Threonine Kinases: A family of serine-threonine kinases that plays a role in intracellular signal transduction by interacting with a variety of signaling adaptor proteins such as CRADD SIGNALING ADAPTOR PROTEIN; TNF RECEPTOR-ASSOCIATED FACTOR 2; and TNF RECEPTOR-ASSOCIATED DEATH DOMAIN PROTEIN. Although they were initially described as death domain-binding adaptor proteins, members of this family may contain other protein-binding domains such as those involving caspase activation and recruitment.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Receptors, TNF-Related Apoptosis-Inducing Ligand: Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.bcl-Associated Death Protein: A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Serpins: A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.JNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.Etoposide: A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.U937 Cells: A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.Genes, bcl-2: The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesMitochondrial Membranes: The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).Recombinant Proteins: Proteins prepared by recombinant DNA technology.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Mice, Inbred C57BLCeramides: Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Receptor-Interacting Protein Serine-Threonine Kinase 2: A RIP serine-theonine kinase that contains a C-terminal caspase activation and recruitment domain. It can signal by associating with other CARD-signaling adaptor proteins and INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.Protein Synthesis Inhibitors: Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Myeloid Cell Leukemia Sequence 1 Protein: A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Autophagy: The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Intracellular Membranes: Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Propidium: Quaternary ammonium analog of ethidium; an intercalating dye with a specific affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits.Receptors, Death Domain: A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Drug Screening Assays, Antitumor: Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.Nucleic Acid Synthesis Inhibitors: Compounds that inhibit cell production of DNA or RNA.Receptors, Tumor Necrosis Factor, Type I: A tumor necrosis factor receptor subtype that has specificity for TUMOR NECROSIS FACTOR ALPHA and LYMPHOTOXIN ALPHA. It is constitutively expressed in most tissues and is a key mediator of tumor necrosis factor signaling in the vast majority of cells. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.Proteolysis: Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Acetylcysteine: The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.Proteasome Endopeptidase Complex: A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.Viral Proteins: Proteins found in any species of virus.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Cell-Free System: A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Endoplasmic Reticulum Stress: Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.Deoxyadenine Nucleotides: Adenine nucleotides which contain deoxyribose as the sugar moiety.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.Lamins: Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Insect Proteins: Proteins found in any species of insect.Microtubule-Associated Proteins: High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Interleukin-1beta: An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.FlavoproteinsCathepsin B: A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Bongkrekic Acid: An antibiotic produced by Pseudomonas cocovenenans. It is an inhibitor of MITOCHONDRIAL ADP, ATP TRANSLOCASES. Specifically, it blocks adenine nucleotide efflux from mitochondria by enhancing membrane binding.Pentanoic AcidsHepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents.Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.L-Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.Protein Kinase C-delta: A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Lamin Type B: A subclass of ubiquitously-expressed lamins having an acidic isoelectric point. They are found to remain bound to nuclear membranes during mitosis.Isatin: An indole-dione that is obtained by oxidation of indigo blue. It is a MONOAMINE OXIDASE INHIBITOR and high levels have been found in urine of PARKINSONISM patients.Keratin-18: A type I keratin found associated with KERATIN-8 in simple, or predominately single layered, internal epithelia.Neuroblastoma: A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)Glutathione: A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.Leupeptins: A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Xenograft Model Antitumor Assays: In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.Mitogen-Activated Protein Kinase 8: A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.Endoplasmic Reticulum: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
MycN sensitizes neuroblastoma cells for drug-induced apoptosis. (1/2233)Amplification of the MYCN gene is found in a large proportion of neuroblastoma and considered as an adverse prognostic factor. To investigate the effect of ectopic MycN expression on the susceptibility of neuroblastoma cells to cytotoxic drugs we used a human neuroblastoma cell line harboring tetracycline-controlled expression of MycN. Neither conditional expression of MycN alone nor low drug concentrations triggered apoptosis. However, when acting in concert, MycN and cytotoxic drugs efficiently induced cell death. Apoptosis depended on mitochondrial permeability transition and activation of caspases, since the mitochondrion-specific inhibitor bongkrekic acid and the caspase inhibitor zVAD-fmk almost completely abrogated apoptosis. Loss of mitochondrial transmembrane potential and release of cytochrome c from mitochondria preceded activation of caspase-8 and caspase-3 and cleavage of PARP. CD95 expression was upregulated by treatment with cytotoxic drugs, while MycN cooperated with cytotoxic drugs to increase sensitivity to CD95-induced apoptosis and enhancing CD95-L expression. MycN overexpression and cytotoxic drugs also synergized to induce p53 and Bax protein expression, while Bcl-2 and Bcl-X(L) protein levels remained unchanged. Since amplification of MYCN is usually associated with a poor prognosis, these findings suggest that dysfunctions in apoptosis pathways may be a mechanism by which MycN-induced apoptosis of neuroblastoma cells is inhibited. (+info)
Identification of an endogenous dominant-negative short isoform of caspase-9 that can regulate apoptosis. (2/2233)Alternatively spliced isoforms of certain apoptosis regulators, such as Bcl-x, Ced-4, and Ich-1, have been shown to play opposing roles in regulating apoptosis. Here, we describe the identification of an endogenous alternatively spliced isoform of caspase-9, named caspase-9b, which lacks the central large subunit caspase domain. Caspase-9b is detectable in many cell lines by PCR and at the mRNA and protein levels. Caspase-9b can interact with the caspase recruitment domain of Apaf-1, and like the active site mutant of caspase-9, it can inhibit multiple forms of apoptosis, including those triggered by oligomerization of death receptors. It can also block activation of caspase-9 and -3 by Apaf-1 in an in vitro cytochrome c-dependent caspase activation assay. These results suggest that caspase-9b functions as an endogenous apoptosis inhibitory molecule by interfering with the formation of a functional Apaf-1-caspase-9 complex. (+info)
Caspase-9 can be activated without proteolytic processing. (3/2233)The recombinant form of the proapoptotic caspase-9 purified following expression in Escherichia coli is processed at Asp315, but largely inactive; however, when added to cytosolic extracts of human 293 cells it is activated 2000-fold in the presence of cytochrome c and dATP. Thus, the characteristic activities of caspase-9 are context-dependent, and its activation may not recapitulate conventional caspase activation mechanisms. To explore this hypothesis we produced recombinant forms of procaspase-9 containing mutations that disabled one or both of the interdomain processing sites of the zymogen. These mutants were able to activate downstream caspases, but only in the presence of cytosolic factors. The mutant with both processing sites abolished had 10% of the activity of wild-type, and was able to support apoptosis, with equal vigor to wild-type, when transiently expressed in 293 cells. Thus caspase-9 has an unusually active zymogen that does not require proteolytic processing, but instead is dependent on cytosolic factors for expression of its activity. (+info)
Tumor necrosis factor alpha regulation of the FAS-mediated apoptosis-signaling pathway in synovial cells. (4/2233)OBJECTIVE: Fas-mediated apoptosis is observed in synoviocytes of patients with rheumatoid arthritis (RA), but not in those of patients with osteoarthritis (OA). The present study was conducted to elucidate the mechanisms that initiate induction of Fas-mediated apoptosis in RA synoviocytes. METHODS: Cultured OA synoviocytes, which are insensitive to Fas-mediated apoptosis in spite of Fas antigen expression, were used in these experiments. Synovial cell proliferation and cytotoxicity studies were performed using MTS and lactate dehydrogenase release assays. Surface expression of Fas antigen was analyzed by flow cytometry. The expression and function of apoptosis-signaling molecules, such as caspase 8 and caspase 3, were examined by immunoblot analysis. RESULTS: Tumor necrosis factor alpha (TNFalpha) induced proliferation of cultured OA synoviocytes. Fas ligation with anti-Fas monoclonal antibody (mAb) resulted in cytotoxic activity against cultured OA synoviocytes that had been pretreated with TNFalpha for 5 days, but not those pretreated for 2 days. In contrast, anti-Fas mAb did not show a cytotoxic effect against untreated cultured OA synoviocytes. A gradual up-regulation of caspase 8 and caspase 3, which played a role in the caspase cascade for Fas-mediated apoptosis, was observed in TNFalpha-treated cultured OA synoviocytes. In addition, Fas ligation to TNFalpha-treated cultured OA synoviocytes induced activation of caspase 8 and caspase 3, with subsequent cleavage of poly(ADP-ribose) polymerase (PARP), a substrate of activated caspase 3. More importantly, Z-IETD-FMK, a caspase 8 inhibitor, and Ac-DEVD-CHO, a caspase 3 inhibitor, almost completely inhibited Fas-mediated apoptosis of TNFalpha-treated cultured OA synoviocytes, whereas Ac-YVAD-CHO, a caspase 1 inhibitor, did not. CONCLUSION: Our results clearly demonstrate that TNFalpha stimulates synovial cells to proliferate as well as sensitizes the cells for Fas-mediated apoptosis, at least in part by up-regulation and activation of caspase 8 and caspase 3. These findings suggest that TNFalpha may be one of the factors providing sensitization of synovial cells to Fas-mediated apoptosis in RA. (+info)
Solution structure of BID, an intracellular amplifier of apoptotic signaling. (5/2233)We report the solution structure of BID, an intracellular cross-talk agent that can amplify FAS/TNF apoptotic signal through the mitochondria death pathway after Caspase 8 cleavage. BID contains eight alpha helices where two central hydrophobic helices are surrounded by six amphipathic ones. The fold resembles poreforming bacterial toxins and shows similarity to BCL-XL although sequence homology to BCL-XL is limited to the 16-residue BH3 domain. Furthermore, we modeled a complex of BCL-XL and BID by aligning the BID and BAK BH3 motifs in the known BCL-XL-BAK BH3 complex. Additionally, we show that the overall structure of BID is preserved after cleavage by Caspase 8. We propose that BID has both BH3 domain-dependent and -independent modes of action in inducing mitochondrial damage. (+info)
Solution structure of the proapoptotic molecule BID: a structural basis for apoptotic agonists and antagonists. (6/2233)Members of the BCL2 family of proteins are key regulators of programmed cell death, acting either as apoptotic agonists or antagonists. Here we describe the solution structure of BID, presenting the structure of a proapoptotic BCL2 family member. An analysis of sequence/structure of BCL2 family members allows us to define a structural superfamily, which has implications for general mechanisms for regulating proapoptotic activity. It appears two criteria must be met for proapoptotic function within the BCL2 family: targeting of molecules to intracellular membranes, and exposure of the BH3 death domain. BID's activity is regulated by a Caspase 8-mediated cleavage event, exposing the BH3 domain and significantly changing the surface charge and hydrophobicity, resulting in a change of cellular localization. (+info)
Nitric-oxide-induced apoptosis in human leukemic lines requires mitochondrial lipid degradation and cytochrome C release. (7/2233)We have previously shown that nitric oxide (NO) stimulates apoptosis in different human neoplastic lymphoid cell lines through activation of caspases not only via CD95/CD95L interaction, but also independently of such death receptors. Here we investigated mitochondria-dependent mechanisms of NO-induced apoptosis in Jurkat leukemic cells. NO donor glycerol trinitrate (at the concentration, which induces apoptotic cell death) caused (1) a significant decrease in the concentration of cardiolipin, a major mitochondrial lipid; (2) a downregulation in respiratory chain complex activities; (3) a release of the mitochondrial protein cytochrome c into the cytosol; and (4) an activation of caspase-9 and caspase-3. These changes were accompanied by an increase in the number of cells with low mitochondrial transmembrane potential and with a high level of reactive oxygen species production. Higher resistance of the CD95-resistant Jurkat subclone (APO-R) cells to NO-mediated apoptosis correlated with the absence of cytochrome c release and with less alterations in other mitochondrial parameters. An inhibitor of lipid peroxidation, trolox, significantly suppressed NO-mediated apoptosis in APO-S Jurkat cells, whereas bongkrekic acid (BA), which blocks mitochondrial permeability transition, provided only a moderate antiapoptotic effect. Transfection of Jurkat cells with bcl-2 led to a complete block of apoptosis due to the prevention of changes in mitochondrial functions. We suggest that the mitochondrial damage (in particular, cardiolipin degradation and cytochrome c release) induced by NO in human leukemia cells plays a crucial role in the subsequent activation of caspase and apoptosis. (+info)
Targeted disruption of caspase genes in mice: what they tell us about the functions of individual caspases in apoptosis. (8/2233)Cysteine proteases of the caspase family are crucial mediators of apoptosis. All mammalian cells contain a large number of caspases. Although many caspases are activated in a cell committed to apoptosis, recent data from caspase gene knockout mice suggest that individual caspases may be involved in the cell and stimulus-specific pathways of cell death. The gene disruption studies also establish the functional hierarchy between two structurally distinct classes of caspases. The present review discusses these recent findings and elaborates on how these mutant mouse models have helped the understanding of the mechanisms that govern programmed cell death in the immune and other systems. (+info)
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Antho 50 induces caspase 3 activation and UHRF1 down-regulation independently of p53 and p73.B CLL cells were incubated with Antho 50 at 75 μg/mL for the ind
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The IUPHAR/BPS Guide to Pharmacology. Caspase 1 - C14: Caspase. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
Caspase 8 enzymatic activity in rat retinas. A: The level of protein expression of caspase 8 in the rat retina was evaluated by western blotting. Diabetes incre
A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE ...
BioAssay record AID 306845 submitted by ChEMBL: Induction of apoptosis in U937 cells assessed as caspase 3 cleavage at 3 uM by Western blot.
The intracellular redox position is intently connected to the levels of professional-inflammatory cytokines, IL-1β, IL-23 and TNF-α which are the major factors of inflammatory responses. IFN-γ has also been shown to be linked with swelling although TNF-α has been researched thoroughly for its function in the inflammatory method and generation of ROS.Maintaining the earlier mentioned information into thought, we evaluated the level of IL-1β and IL-seventeen employing ELISA even though IFN-γ, IL-23 and TNF-α mRNA expression fold transform was identified utilizing qRT-PCR. We located that IL-1β ranges had been considerably larger in the two diabetic teams as in MEDChem Express 415903-37-6 contrast to the wholesome handle topics. The IL-1β is typically expressed by in-filtering macrophages, once activated they synthesize larger volume of nitric oxide as well. Curiously, there have been outstanding discrepancies in both NO and cytokine levels in the patients of higher age teams with glucose ...
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Caspase 3 antibody LS-C88630 is a biotin-conjugated rabbit polyclonal that binds human, mouse, rat, bovine, dog, hamster, pig, rabbit, and sheep caspase 3 (also known as CASP3). Caspase 3 antibody is validated for use in IHC-paraffin, immunoprecipitation, and western blot.
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This video will show you how to perform an apoptosis assay using adherent cells on the Celigo image cytometer using caspase 3/7 and Hoechst reagents.
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Induction of apoptosis and NF-kB activation by Apaf-1/Nod1 family members and DD proteins (Inohara et al., 2000). The more recent study suggested that IKKgamma binds to the site in C-terminal regulatory region of IKKbeta which is located after the HLH motif. Images ...
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Apoptosis is a controlled form of cellular demolition, catalyzed by a family of cysteine proteases called caspases. In response to diverse proapoptotic stimuli, caspase-9 is recruited and activated within an oligomeric complex called the apoptosome. The apoptosome drives autocatalytic processing of caspase-9, triggering a proteolytic caspase cascade that results in the biochemical and morphological changes characteristic of cell death. It is unclear why caspase-9 undergoes autocatalytic processing following apoptosome recruitment, because interdomain processing is dispensable for caspase-9 activity. A study has shed light on this issue by demonstrating that caspase-9 processing within the apoptosome promotes its displacement from the complex, leading to inactivation of this protease. Thus, autoprocessing of caspase-9 within the apoptosome serves as a "molecular timer" that limits the proteolytic activity of this complex through displacement of bound caspase-9 molecules. This timer mechanism may ...
Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene. CASP6 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. Caspase-6 has known functions in apoptosis, early immune response and neurodegenration in Huntingtons and Alzheimers disease. This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Caspase 6 can also undergo self-processing without other members of the caspase family. Alternative ...
Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the CASP3 gene. CASP3 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. The CASP3 protein is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 6 and 7; and the protein itself is processed and activated by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimers disease. Alternative splicing of this gene results in two ...
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Active Caspase 2 FITC Staining Kit (ab65612). Active caspase 2 detection in living cells by flow, microscopy or fluorescent plate reader.
BioAssay record AID 675053 submitted by ChEMBL: Induction of apoptosis in human SW620 cells assessed as activation of caspase 3/7 at 100 uM after 24 hrs by luminescence assay.
Human caspase 2 ELISA kit can be used for detecting in vitro quantitative levels of caspase-2 (CASP2) in human serum, cell culture supernatant, plasma, tissue
Read independent reviews on Caspase Fluorometric Substrate Set II Plus from AMS Biotechnology (Archived Products) on SelectScience
72 products from 18 suppliers. Compare and order Caspase 8 ELISA Kits. View citations, images, detection ranges, sensitivity, prices and more. Recommended products for the most popular species. Our scientists will help you find the right ELISA kit for your needs.
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Assay Kits , Caspase Assay Kits , SensoLyte AFC Caspase Profiling Kit *Fluorimetric*; Caspases play important roles in apoptosis and cell signaling. They are also identified as drug-screening targets. AFC-based substrates yield blue fluorescence upon protease cleavage. They are widely used to monitor caspase activity. The SensoLyte Caspase Profiling Kit contains a series of AFC-based peptide substrates (Ex/Em=380 nm/500 nm) as fluorogenic indicators for assaying caspase protease activities. The kit contains a well-designed plate in which a series of AFC-based caspase substrates are coated with both positive and negative controls. It provides the best solution for profiling caspases or caspase inhibitors. The kit contains: A 96-well plate coated with a series of AFC-based caspase substrates along with various controls* Cell lysis buffer Assay buffer AFC (fluorescence reference standard for calibration) A detailed protocol A detailed protocol
Caspase inhibition is effective in minimizing nucleosome accumulation in key cortical cultures stimulated by TNF and thrombin. In contrast, the exact same effect is simply not observed in differentiated PC12 cells. In PC12 cells TNF induced LDH release is decreased by caspase inhibition. For the reason that TNF remedy induces both LDH release and nucleosome accumulation in PC12 cells, caspase inhibition could possibly enrich cell survival below disorders that induce a mixed apoptotic necrotic response. Pytlowany and colleagues demonstrate that In PC12 cells NO released from SNP decreases cell viability inside a time and concentration dependent method, with a increased concentration of NO leading to immediate and sustained lower in cell survival with no evoking a corresponding immediate activation of caspase three . In the recent review we locate that NO created by 0.5 mM SNP activates caspase three inside a longer time frame ...
TY - JOUR. T1 - Protective effect of resveratrol against caspase 3 activation in primary mouse fibroblasts. AU - Ulakcsai, Zsófia. AU - Bagaméry, Fruzsina. AU - Vincze, István. AU - Szöko, Éva. AU - Tábi, Tamás. PY - 2015/1/1. Y1 - 2015/1/1. N2 - Aim: To study the effect of resveratrol on survival and caspase 3 activation in non-transformed cells after serum deprivation. Methods: Apoptosis was induced by serum deprivation in primary mouse embryonic fibroblasts. Caspase 3 activation and lactate dehydrogenase release were assayed as cell viability measure by using their fluorogenic substrates. The involvement of PI3K, ERK, JNK, p38, and SIRT1 signaling pathways was also examined. Results: Serum deprivation of primary fibroblasts induced significant activation of caspase 3 within 3 hours and reduced cell viability after 24 hours. Resveratrol dose-dependently prevented caspase activation and improved cell viability with 50% inhibitory concentration (IC50) = 66.3 ± 13.81 μM. It also reduced ...
Fluorescent Dyes , Enzyme Detection Reagents , Caspase 3 (Apopain) Substrate 1r-z, fluorogenic; Rh110 (rhodamine 110)-derived caspase substrates are probably the most sensitive indicators widely used for the fluorimetric detection of various caspase activities. Cleavage of Rh110 peptides by caspases generates strongly fluorescent Rh110 that is monitored fluorimetrically at 510-530 nm with excitation of 488 nm, the most common excitation light source used in fluorescence instruments.; Caspase-3 substrate and caspase-7 substrate; (Z-DEVD)2-Rh110; z-(Asp-Glu-Val-Asp)2-Rh110
Caspase 3/7 Glo assay from Promega - posted in Apoptosis, Necrosis and Autophagy: Hello all, I recently purchased a Caspase 3/7 Glo assay kit from Promega for apoptosis detection.My assay was done with HEK293 cells which were stimulated with Etoposide.I performed the assay exactly described in the protocol,and detected the luminescence with our Luminoskan Ascent luminometer. Unfortunately, in my assay I observed no induction of caspase activity and that the highest reading was equal to the...
Severn Biotech, Limited SBP0058 - Caspase 1 Inhibitor Ac-YVAD aldehyde - SBP0058 - Caspase 1 Inhibitor Ac-YVAD aldehyde MW: 492.5 Ac-Tyr-Val-Ala-Asp-CHO A specific reversible inhibitor of caspase 1 (ICE, Interleukin 1ß Converting Enzyme) Thornberry N.A. et al. (1992) Nature 356, 768; Molineaux S.M. et al. (1993) Proc. Natl. Acad. Sci. USA 90, 1809; Walker N.P.C. et al. (1994) Cell 78, 343; Wilson K.P. et al. (1994) Nature 370, 270;
Generic Caspase Activity Assay Kit (Fluorometric - Green) (ab112130). Detect generic caspase activation in live cells with green TF2-VAD-FMK substrate.
Death receptor (DR) ligation can lead to divergent signaling pathways causing either caspase-mediated cell death or cell proliferation and inflammation. These variations in cellular fate are determined by adaptor proteins that are recruited to the DR signaling complex. FLICE inhibitory protein (FLIP) is an established inhibitor of caspase-8-mediated apoptosis, and it is also involved in NF-kappa B
Caspase Substrate Assay Kit (Colorimetric) is used for assaying activities of members of caspase 1/2/3/5/6/8/9. (KA3698) - Products - Abnova
Kumar, A.P., Chang, M.K.X., Clement, M.-V., Fliegel, L., Pervaiz, S. (2007). Oxidative repression of NHE1 gene expression involves iron-mediated caspase activity. Cell Death and Differentiation 14 (10) : 1733-1746. [email protected] Repository. https://doi.org/10.1038/sj.cdd. ...
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F CD8+ T lymphocytes before operation, but this difference was not statistically BI 78D3 Significant (P.0.05). The percentages of CD8+ T lymphocytes in the
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Plasmid pcDNA-Caspase 12 from Dr. Junying Yuans lab contains the insert Caspase 12 and is published in Nature. 2000 Jan 6. 403(6765):98-103. This plasmid is available through Addgene.
Caspases are a conserved family of cysteine proteases. They play diverse roles in inflammatory responses and apoptotic pathways. Among the caspases is a subgroup whose primary function is to initiate apoptosis. Within their long prodomains, caspases-2, -9 and -12 contain a caspase activation and recruitment domain while caspases-8 and -10 bear death effector domains. Activation follows the recruitment of the procaspase molecule via the prodomain to a high molecular mass complex. Despite sharing some common features, other aspects of the biochemistry, substrate specificity, regulation and signaling mechanisms differ between initiator apoptotic caspases. Defects in expression or activity of these caspases are related to certain pathological conditions including neurodegenerative disorders, autoimmune diseases and cancer ...
A short pro-domain caspase that plays an effector Role in Apoptosis. It is activated by Initiator Caspases such as Caspase 3 and Caspase 10. Several Isoforms of this protein exist due to multiple Alternative Splicing of its Messenger RNA ...
Background: The Division of Cancer Treatment and Diagnostics/National Cancer Institute has embarked on development of a multiplex panel of biomarkers of the apoptosis pathway to support proof-of-mechanism studies of investigational agents targeting apoptosis. The selected biomarkers provide quantitative estimate of the commitment, onset, and induction of apoptosis, especially the intrinsic apoptosis pathway. This study updates progress in development of the multiplex panel.. Methods: The immunoassays are built on the Luminex® xMAP multiplex technology platform using magnetic bead capture. The current panel included caspase-3, Lamin-B, Survivin, and markers involved in mitochondrial apoptosis including oligomeric forms of BCL2 family proteins. Calibrators for oligomeric proteins, which are formed in vivo by the non-covalent association of BH3 domain proteins, are developed as synthetic recombinant fusion proteins. The panel is designed for analysis of biomarkers in fractionated cell lysates ...
SWISS-MODEL Repository entry for Q297U0 (FADD_DROPS), Fas-associated death domain protein. Drosophila pseudoobscura pseudoobscura (Fruit fly)
Click to launch & play an online audio visual presentation by Prof. Guy Salvesen on Natural caspase inhibitors, part of a collection of online lectures.
The Caspase-3 and -8 Colorimetric Assays kits measure the proteolytic cleavage of the chromophore p-nitroanilide (pNA) by caspase- 3 or -8.
The Caspase-3 and -8 Colorimetric Assays kits measure the proteolytic cleavage of the chromophore p-nitroanilide (pNA) by caspase- 3 or -8.
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|strong|Rabbit anti caspase-9 p10 antibody|/strong| recognizes caspase-9, a member of the cysteine-aspartic acid protease family. The active form of caspase-9 is generated by cleavage of the pro-caspa…
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Detail záznamu - Role of Caspases and CD95/Fas in the Apoptotic Effects of a Nucleotide Analog PMEG in CCRF-CEM Cells - Detail záznamu - Knihovna Akademie věd České republiky
Caspase 12 antibody [14F7] (caspase 12) for ICC/IF, IHC, IP, WB. Anti-Caspase 12 mAb (GTX10455) is tested in Mouse, Rat samples. 100% Ab-Assurance.
Research tested and proven Caspase-10/b-Flice 2 antibody. Antibody is guaranteed to work in western blot applications and is reactive in human and mouse.
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The development and growth of aneurysms involve the complex events of arterial wall cells remodeling (38). Previous studies have demonstrated that apoptosis is involved in the pathogenesis of aneurysms (6,7). However, the molecular mechanisms underlying the stimulation of apoptosis in the mouse IA model remains unknown.. To investigate the apoptotic events of IA mice model, the present study investigated the mRNA expression of caspases associated with the mitochondrial apoptotic pathway, including caspase-3, −8 and −9. The activation of caspases serves an essential role during the process of apoptosis (39), which may be caused by an extrinsic or intrinsic pathway, which lead to a terminal common pathway (40). Caspase-8 activation is involved in the extrinsic pathway and caspase-9 is involved in the intrinsic pathway. In the mitochondrial pathway, the release of Cyt-c constitutes an apoptotic complex, which subsequently results in the activation of caspase-9. The activation of caspase-8 and ...
The illustration depicts a wild type mouse and a littermate mutant mouse expressing a constitutive serine phosphorylation mutation in Fas-Associated Death Domain (FADD-D). FADD-D mice exhibit reduced body size. The corresponding confocal images show mislocalization of FADD-D protein. Activated T cells from either wild type or FADD-D mice were stained with FADD antibody (green and pink, respectively) and DAPI (blue).
Evidence suggests that the signalling events which occur after apoptotic stimulation, define two basic mechanisms for the induction of apoptosis. The first is dependent on signalling via the mitochondria and the second is dependent upon signalling directly from the death receptors. After induction of apoptosis, there is a convergence in signalling at the level of caspase activation and subsequent biochemical and morphological changes. Therefore the efficacy of various inhibitors of apoptosis is dependent upon the initiating signal. In order to understand the apoptotic pathway, the mechanisms by which these inhibitors regulate chemical- and receptor-mediated apoptosis must be understood. The anti-apoptotic oncoprotein, Bcl-2, was shown to inhibit both staurosporine and Fas-mediated apoptosis in a manner which was partially dependent upon the level of Bcl-2 protein expressed. During both staurosporine and Fas-induced apoptosis Bcl-2 acted downstream of caspase-8 activation. High levels of Bcl-2 ...
... , Authors: Frank A. Kruyt. Published in: Atlas Genet Cytogenet Oncol Haematol.
Caspase-1, originally called ICE, was the first mammalian analogue of the Caenorhabditis elegans death genes to be identified.11 Like all caspases, it is expressed as a proform, which is activated through proteolytic cleavage of an amino-terminal 11-kDa prodomain to release p20 and p10 subunits. Active caspase-1/ICE consists of a (p20/p10)2 tetramer, which is sufficient to process precursor IL-1β9,12-14 and, in at least some cell types, to induce apoptosis.16 Additionally, the prodomain has been postulated to have independent proapoptotic activity by enhancing death receptor-mediated caspase-8 activation.39 Although caspase-1 has conventionally been regarded as a proinflammatory, not a proapoptotic, caspase,10-12 it has been observed to induce or amplify apoptosis in tissue culture models.15,16. Regulated expression of caspase-1 in cardiac hypertrophy,17 the dilated cardiomyopathy of TNF-α overexpression,19 ischemia/infarction,21 and endotoxin-induced myocardial dysfunction18 prompted our ...
PTK787 2HCl and -7 (Lakhani et al. 2006 offers contributed to your knowledge of the physiological tasks of the caspases significantly. Oddly enough C57BL/6 mice deficient for both caspase-3 and -7 perish shortly after delivery while mice missing only caspase-3 or -7 have a normal life span and display a limited apoptotic phenotype in this genetic background (Lakhani et al. 2006 Leonard et al. 2002 This points to the functional redundancy between caspase-3 and -7 during embryogenesis. However several observations suggest that this overlap is not complete and that caspase-3 and -7 also fulfill non-redundant roles in apoptosis. For instance eye lenses of caspase-7 knockout mice are grossly normal whereas those of caspase-3 deficient mice display marked cataracts at the anterior lens pole (Zandy et al. 2005 Further support for this notion stems from biochemical studies demonstrating that caspase-3 and -7 exhibit differential activities toward multiple protein substrates with caspase-7 being more ...
Caspases, aspartate-specific cysteine proteases, have fate-determining roles in many cellular processes including apoptosis, differentiation, neuronal remodeling, and inflammation (for review, see Yuan & Kroemer, 2010). There are a dozen caspases in humans alone, yet their individual contributions toward these phenotypes are not well understood. Thus, there has been considerable interest in activating individual caspases or using their activity to drive these processes in cells and animals. We envision that such experimental control of caspase activity can not only afford novel insights into fundamental biological problems but may also enable new models for disease and suggest possible routes to therapeutic intervention. In particular, localized, genetic, and small-molecule-controlled caspase activation has the potential to target the desired cell type in a tissue. Suppression of caspase activation is one of the hallmarks of cancer and thus there has been significant enthusiasm for generating ...
This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein can undergo autoproteolytic processing and activation by the apoptosome, a protein complex of cytochrome c and the apoptotic peptidase activating factor 1; this step is thought to be one of the earliest in the caspase activation cascade. This protein is thought to play a central role in apoptosis and to be a tumor suppressor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013 ...
... ; Caspase-9 precursor (EC 3.4.22.-) (CASP-9) (ICE-like apoptotic protease 6) (ICE-LAP6) (Apoptotic protease Mch-6) (Apoptotic protease activating factor 3) (APAF-3). [Source:Uniprot/SWISSPROT;Acc:P55211 ...
Cell death via apoptosis is a key cellular function triggered by the cell death receptor family and their ligands which signal through downstream adaptor molecules and the caspase protease family.
The importance of the presented study lies in several key findings. First, our mechanistic knowledge of how the alternative splicing of caspase 9 is regulated has been expanded by our identification of a novel RNA cis-element via which SRSF1 (ASF/SF2) enhances the inclusion of the exon 3,4,5,6 cassette. Furthermore, SRSF1 was shown to specifically interact with this RNA cis-element, and regulate the alternative splicing of caspase 9 via this novel RNA cis-element. Second, we showed that the alternative splicing of caspase 9 is a relevant therapeutic target as shown by direct manipulation of this splicing cascade having significant effect on the sensitivity NSCLC cells to clinically relevant chemotherapeutics. Finally, one of the major findings of the report is our data showing that the synergism of erlotinib combination therapy is in part via modulation of the alternative splicing of caspase 9.. In regard to the RNA cis-element that specifically interacts with SRSF1, a purine-rich RNA ...
IAP (Inhibitors of Apoptosis) is a family of functionally and structurally related proteins, which serve as endogenous inhibitors of programmed cell death (apoptosis). A common feature of all IAPs is the presence of a BIR in one to three copies. The human IAP family consists of 8 members, and IAP homologs have been identified in numerous organisms. The members of the IAPs included IAPs, Cp-IAP, Op-IAP, XIAP, c-IAPl, C-IAP2, NAIP, Livin and Survivin. The best characterized IAP is XIAP, which binds caspase-9, caspase-3 and caspase 7, thereby inhibiting their activation and preventing apoptosis. Also cIAP1 and cIAP2 have been shown to bind caspases, although how the IAPs inhibit apoptosis mechanistically at the molecular level is not completely understood.. ...
The Pa-PDT induced p-JNK caused down-regulation of the pro-apoptotic protein bcl-2 that facilitates the collapse of mitochondrial membrane and eventually initiates the intrinsic apoptotic pathway ...
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Caspase-10 Assay Kit (Colorimetric) is used for detecting the activity of caspases that recognize the sequence AEVD using colorimetric method. (KA0730) - Products - Abnova
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2 Department of Radiation Oncology, University Hospital Zurich, CH-8091 Zurich, Switzerland [S. R., C. G., S. B., M. P.]; Laboratory for Biochemistry, Federal Institute of Technology, 8091 Zurich, Switzerland [S. R., K. W.]; Novartis Pharma Inc., 4002 Basel, Switzerland [D. F.]; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 [M. S. S., S. W. L.] Abstract. Caspases are a family of cysteine proteases that constitute the apoptotic cell death machinery. We report the importance of the cytochrome c-mediated caspase-9 death pathway for radiosensitization by the protein kinase C (PKC) inhibitors staurosporine (STP) and PKC-412. In our genetically defined tumor cells, treatment with low doses of STP or the conventional PKC-specific inhibitor PKC-412 in combination with irradiation (5 Gy) potently reduced viability, enhanced mitochondrial cytochrome c release into the cytosol, and specifically stimulated the initiator caspase-9. Whereas treatment with each agent alone had a minimal ...
Silibinin, a natural flavonolignan, induces apoptosis in human bladder transitional-cell papilloma RT4 cells both in vitro and in vivo; however, mechanisms of such efficacy are not completely identified. Here, we studied the mechanisms involved in silibinin-induced apoptosis of RT4 cells having intact p53. Silibinin increased p53 protein level together with its increased phosphorylation at serine 15, activated caspase cascade and caused Bid cleavage for apoptosis. Silibinin-caused p53 activation was mediated via ATM-Chk2 pathway, which in turn induced caspase 2-mediated apoptosis. Pifithrin-α, a p53 inhibitor, reversed silibinin-induced caspase activation including caspase 2; however, caspase 2 inhibitor also reversed p53 phosphorylation suggesting a bidirectional regulation between them. Further, silibinin caused a rapid translocation of p53 and Bid into mitochondria leading to increased permeabilization of mitochondrial membrane and cytochrome c release into the cytosol. JNK1/2 activation was ...
In this study, we define a critical role for Grx in TNF-α-mediated caspase-3 activation through regulation of caspase-3 cleavage and glutathiolation. Data to support this notion include (1) caspase-3 cleavage by TNF-α inversely correlated with glutathiolation; (2) TNF-α activated Grx. In Grx knock-down cells, TNF-α-induced apoptosis was attenuated and caspase-3 cleavage was significantly reduced, concomitant with increased caspase-3 glutathiolation; (3) enhanced caspase-3 cleavage by Grx overexpression was reversed by a thioltransferase inactive Grx (C22S); (4) in vitro glutathiolation experiments showed that caspase-3 cleavage by caspase-8 was inversely correlated with caspase-3 glutathiolation; (5) mutations of cysteines (C184 and C220) in caspase-3 show significant increase in cleavage; and (6) Grx binds caspase-3. Our data suggest a model in which TNF-α activates Grx, Grx deglutathiolates caspase-3, and then Grx dissociates from caspase-3, leading to caspase-3 activation. The present ...
Apoptotic signaling is altered at many loci in cancer cells. Although many tumors develop resistance to cytochrome c-induced apoptosis, we have discovered that breast cancer cells exhibit a unique hypersensitivity to cytochrome c-induced apoptosis. Interestingly, this sensitivity is not due to changes in core apoptosomal proteins ( 44) but is due to a PHAPI-mediated posttranslational event that enhances the recruitment of caspase-9 to the Apaf-1 CARD. These findings have the potential to affect breast cancer chemotherapy through the development of apoptosome activators or cytochrome c mimetics as shown, in principle, by the fact that malignant mammary epithelial cells could be more easily killed by cytosolic cytochrome c than their normal counterparts.. PHAPI-mediated increase in caspase activation in breast cancer. Whereas many inhibitory signaling pathways converge on the apoptosome, there are very few physiologic/pathologic examples of enhanced apoptosome activation. Our data suggest that ...
Activation of Fas receptor by Fas ligand causes caspase 8 activation and apoptosis in cells and is an important mechanism by which normal tissue homeostasis and function are maintained. Activation of caspase 8 is preceded by the formation of a death-inducing signalling complex (DISC), and a number of redundant mechanisms regulate DISC formation in vivo. Fas receptor is widely expressed in tissues, and dysfunction of the regulatory mechanisms in Fas receptor signalling has been reported in several diseases including autoimmune disease and cancer. This review aims to identify and discuss the various mechanisms employed by cells to alter their sensitivity to Fas-mediated apoptosis by regulating DISC formation. We also discuss a number of defects identified with Fas receptor signalling and the associated pathologies.
Caspases are normally suppressed by IAP (inhibitor of apoptosis) proteins (see "Controlling the Caspases", by Stephen W. Fesik and Yigong Shi, in Science, Vol. 294, No. 5546, p. 1477, November 16, 2001). When a cell receives an apoptotic stimulus, IAP activity is relieved after SMAC (Second Mitochondria-derived Activator of Caspases, or its mouse homolog, called DIABLO), a mitochondrial protein, is reléased into the cytosol. SMAC binds to IAPs, and in doing so "inhibits the inhibitors", effectively preventing them from arresting the apoptotic process. But before we go on to a short description of how SMAC is reléased, lets take a look at two well-studied extrinsically induced apoptotic processes: the TNF and the Fas pathways. Keep in mind, however, that both activating and inhibiting factors are present at éach step of these pathways. Tumor necrosis factor (TNF), a 157 amino acid inter-cellular signaling molecule (cytokine) produced mainly by activated macrophages, and is the major extrinsic ...
... evolutionarily, provides been suggested as a factor in maintenance of chromosomal tumour and balance reductions. can either arise from different structural lesions, such simply because mutations, chromosomal translocations or deletions, or can result from statistical changes where cells lose or gain copies of entire chromosomes (aneuploidy).3 NVP-BEP800 As the most common chromosome abnormality in individuals, aneuploidy is the most common chromosome abnormality in individuals, is the trigger of many congenital delivery flaws and is found in the majority of good tumours.4 It is also regarded a key underlying factor to tumor onset and treatment. Aneuploidy occurs from extravagant mitotic occasions, including problems in centrosome quantity, kinetochore-microtubule accessories, spindle-assembly gate (SAC), chromosome telomeres or cohesion. 4 Aberrant mitotic police arrest systems normally result in cell loss of life by apoptosis, ...
Background The fundamental oil (EO) of L. particular caspase inhibitors showed that activation of caspase-8 was following and reliant towards the activation of caspases-9 and -3. In addition, the fundamental essential oil triggered a disruption from the mitochondrial transmembrane potential (m), improved the discharge of cytochrome towards the cytosol, and modified the manifestation of certain people of Bcl-2 family members (Bcl-2, Bax and Bet), Apaf-1 and XIAP. Oddly enough, low dosages of AVO-b and AVO-1 induced apoptosis in a variety of malignancy cellular lines also, however, not in noncancerous cellular material. Conclusions The full total outcomes demonstrate how the EO-induced apoptosis in HL-60 cellular material is definitely mediated by caspase-dependent pathways, concerning caspases-3, -9, and -8, that are initiated by Bcl-2/Bax/Bid-dependent lack of 173039-10-6 manufacture m resulting in launch of cytochrome towards the cytoplasm to activate the caspase cascade. The discovering that ...
Background The fundamental oil (EO) of L. particular caspase inhibitors showed that activation of caspase-8 was following and reliant towards the activation of caspases-9 and -3. In addition, the fundamental essential oil triggered a disruption from the mitochondrial transmembrane potential (m), improved the discharge of cytochrome towards the cytosol, and modified the manifestation of certain people of Bcl-2 family members (Bcl-2, Bax and Bet), Apaf-1 and XIAP. Oddly enough, low dosages of AVO-b and AVO-1 induced apoptosis in a variety of malignancy cellular lines also, however, not in noncancerous cellular material. Conclusions The full total outcomes demonstrate how the EO-induced apoptosis in HL-60 cellular material is definitely mediated by caspase-dependent pathways, concerning caspases-3, -9, and -8, that are initiated by Bcl-2/Bax/Bid-dependent lack of 173039-10-6 manufacture m resulting in launch of cytochrome towards the cytoplasm to activate the caspase cascade. The discovering that ...
The present study examined levels of various components of the cell death machinery and drug sensitivity of 60 human cancer cell lines to anticancer drugs. With the exception of procaspase-3, which was undetectable in MCF-7 cells, caspases-2, -3, -6, -7, -8, and -9, as well as Apaf-1, were detectable in all 60 cell lines. Although these components of the cell death machinery varied widely in abundance, strong correlations between levels of Apaf-1 or procaspase-2, -3, -6, -8, or -9 and sensitivity to any class of antineoplastic agent were not observed. These results, although negative, have several important implications.. The attempt to correlate drug sensitivity with levels of various components of the cell death machinery was prompted by previous studies indicating that drug-induced apoptosis is markedly diminished when certain key components of the core cell-death machinery, particularly Apaf-1, procaspase-9, or procaspase-3, are genetically or functionally deleted (36, 37, 38 , 58 , 88 , 99) ...
As previously reported, recombinant xEIAP/XLX is rapidly degraded by at least two distinct, consecutively acting proteolytic systems [11, 14]. Within 2 h incubation, xEIAP/XLX is significantly degraded in both CSF-arrested and interphase egg extracts in a C-terminal RING finger-dependent manner. Subsequently, spontaneous cytochrome c-induced caspase activation begins after 4 h incubation in interphase egg extracts (apoptotic egg extracts), and the remaining xEIAP/XLX is cleaved by the activated caspases at yet unidentified site(s). This caspase activation is delayed or suppressed in CSF-arrested egg extracts by a p42MAPK-dependent pathway [7-11]. We found that the electrophoretic mobilities of recombinant 6XHis-tagged (6XHis-FL) and MBP-tagged (MBP-FL) xEIAP/XLX slightly decreased during incubation in CSF-arrested but not interphase egg extracts (Fig. 1B), whereas those of other BIR family proteins (xSurvivin1/xBIR1, xSurvivin2/SIX, and xXIAP) did not (data not shown). However, the rapid ...
Lee Ann, I asked a similar question months ago and got no help other than a hearty good luck! :-) So I did some investigating and can offer two IHC suggestions: Anti-activated Caspase-3. Cleavage (activation) of procaspase-3 (CPP32, apopain, YAMA) irreversibly commits the cell to the caspase cascade and cell death via apoptosis. Antibodies are available that react only with the Caspase-3 cleavage fragment(s) and not procaspase-3. Similarly, anti-PARP p85 fragment. PARP (poly ADP-ribose) is the nuclear substrate for activated Caspase-3 which cleaves PARP into the 25kDa and 85kDa fragments. Antibodies are available that react specifically with the PARP 85kDa fragment. Neither of these should stain necrotic cells as far as I know. As you point out TUNEL labeling of fragmented DNA doesnt discriminate between the two processes. I wish someone would find a protein expressed only by necrotic cells. Regards, Brett Brett M. Connolly, Ph.D. Merck Research Laboratories Department of Pharmacology ...
caspase-3 Antibody (E-8) is a mouse monoclonal IgG2a that detects human caspase-3 and full length procaspase-3 by WB and Staining. 488 citations
Chemical-registry-number] 0 / Antigens, CD95; 0 / BH3 Interacting Domain Death Agonist Protein; 0 / BID protein, human; 0 / Carrier Proteins; 9007-43-6 / Cytochromes c; EC 3.4.22.- / CASP3 protein, human; EC 3.4.22.- / CASP8 protein, human; EC 3.4.22.- / CASP9 protein, human; EC 3.4.22.- / Caspase 3; EC 3.4.22.- / Caspase 8; EC 3.4.22.- / Caspase 9; EC 3.4.22.- / ...
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Z-VAD-FMK is a cell-permeable, irreversible pan-caspase inhibitor, blocks all features of apoptosis in THP.1 and Jurkat T-cells.
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One of the first two classes introduced with Diablo 3, the Barbarian is a powerful melee class that uses fury as a resource. The Barbarian is the only one of the first five characters to use strength for a mainstat and has consistently ranked as one of (or the) most popular class during the first year of Diablo 3.
It might share the Diablo name with the SV and VT that debuted the same year, but this 1999 Lamborghini Diablo GT was an entirely...
This device includes a centrifugal cup or bowl (2) rotating at the speed of 2ω around its revolving axis, a separation chamber (3) connected to the center of this cup or bowl (3) by three channels (4, 5, 6) integral to three flexible tubes (4 a , 5 a , 6 a) forming open loops driven at the speed of ω while their second respect extremities, coaxially located with respect to the first ones, are stationary. The radius and height of this cup or bowl (2) are between 25-50 mm, and 75 to 125% respectively of this radius; its angular speed 2ω is |500 rad/sec to ensure a flow rate for the liquid to be centrifuged of at least 100 ml/min. The material and the dimensions of the tubes (4 a , 5 a , 6 a) are chosen so that the traction force exerted on them is |0.7 N/mm2, its elasticity module is |5 N/mm2 and its rupturing resistance to alternate bending is higher than 1.5 N/mm2.
The cockatoo might be tiny, but he sure is mighty throwing those coins across the room. Eric is a bit feisty too - talking back to his mom, and repeating what she says as she tells him to stop making a mess. The video is just too cute, and any parent will laugh in solace with poor Erics mom - knowing exactly what she is going through dealing with an unruly child ...
Caspase-3 plays a key role in initiation of cellular events during the apoptotic process. PromoKines Caspase-3 and Caspase-7 Immunoassay Kits allow quantification of the specific activity of caspase-3 and -7, respectively. Since caspase-3 and -7 share the same target substrate sequence (DEVD), it is difficult to differentiate the cleavage activity attributed by these two caspases in vitro. Thus, the assays utilize caspase-3 or -7 specific antibodies to capture the activated caspase-3 or -7 in cell lysate. Specific activity of caspase-3 or -7 can then be analyzed using the common caspase-3/7 substrate DEVD-AFC. The assay system ensures absolute specific detection of only caspase-3 or caspase-7 activity in apoptotic samples. Other caspases and non-specific proteases are not detected.. ...
Excess progenitor cell proliferation that leads to gross brain abnormalities is often lethal, as seen in caspase-3 or caspase-9 ... Kuida, K (1998). "Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94: 325-337 ... to cells (such as feedback from neighbors, stress or DNA damage), mitochondria release caspase activators that trigger the cell ... Kroemer G, Martin SJ (2005). "Caspase-independent cell death". Nature Medicine. 11 (7): 725-30. doi:10.1038/nm1263. PMID ...
"Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94 (3): 325-37. doi:10.1016/ ... 297 (5580): 365-9. Bibcode:2002Sci...297..365C. doi:10.1126/science.1074192. PMID 12130776.. ...
... hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner". The Journal of Cell Biology. ... Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 ... Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 ... Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. Alternative splicing results ...
... activating caspase-9 and eventually inducing apoptosis via caspase-3 activation. Hsp70 inhibits this process by blocking the ... It does not bind directly to the procaspase-9 binding site, but likely induces a conformational change that renders procaspase- ... 9 binding less favorable. Hsp70 is shown to interact with Endoplasmic reticulum stress sensor protein IRE1alpha thereby ... "Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome". Nature Cell ...
2005) XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs. EMBO J 24: 645-655 ... 2006) The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases. J Biol Chem 281: 3254-3260 Pop C, ... His research focuses on proteases and their inhibitors in humans, with particular emphasis on the caspases of the apoptotic ... 2006) The apoptosome activates caspase-9 by dimerization. Mol Cell 22: 269-275 Eckelman BP, Salvesen GS. ( ...
Caspase recruitment domain-containing protein 9 is an adaptor protein that in humans is encoded by the CARD9 gene. CARD9 is a ... "Entrez Gene: CARD9 caspase recruitment domain family, member 9". Gross O, Gewies A, Finger K, Schäfer M, Sparwasser T, Peschel ... "CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-kappa B". J. ... "CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-kappa B". J. ...
Rho inactivation can activate caspase-3 and caspase-9; two key components of the apoptotic pathway. TcdA has been linked to ... 50 (7): 613-9. PMID 11444771. Kuehne SA, Cartman ST, Heap JT, Kelly ML, Cockayne A, Minton NP (October 2010). "The role of ... 62 (2): 384-9. PMC 186119 . PMID 8300199. Hecht G, Pothoulakis C, LaMont JT, Madara JL (November 1988). "Clostridium difficile ... mitochondrial membrane disruption and release of cytochrome C through caspase activation and Rho inactivation, further ...
... the TAK1/JNK1 signaling cascade and caspase inhibition.». Mol. Cell. Biol. 22 (6): 1754-66. DOI:10.1128/MCB.22.6.1754-1766.2002 ... Neuronal apoptosis-inhibitory protein does not interact with Smac and requires ATP to bind caspase-9.». J. Biol. Chem. 279 (39 ... NAIP interacts with hippocalcin and protects neurons against calcium-induced cell death through caspase-3-dependent and - ... J. 381 (Pt 1): 213-9. DOI:10.1042/BJ20031506. PMID 15107016.. *. Davoodi J, Lin L, Kelly J, et al. (2004). « ...
There are two types of caspases: initiators and effectors. Initiator caspases cleave inactive forms of effector caspases. This ... Pharmacological approaches involve inhibitors of caspase activity, and caspase inhibition might delay cell death in the ... This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from the mitochondrial ... Caspases (cysteine-aspartic acid proteases) cleave at very specific amino acid residues. ...
... has been shown to interact with: ALS2CR2, Caspase 3. Caspase 7, Caspase-9, Diablo homolog HtrA serine peptidase 2, MAGED1 ... Caspases are the enzymes primarily responsible for cell death. XIAP binds to and inhibits caspase 3, 7 and 9. The BIR2 domain ... When inhibiting caspase-3 and caspase-7 activity, the BIR2 domain of XIAP binds to the active-site substrate groove, blocking ... This allows normal caspase activity to proceed. The binding process of Smac/DIABLO to XIAP and caspase release requires a ...
BCR-ABL has also been implicated in preventing caspase 9 and caspase 3 processing, which adds to the inhibitory effect. ... The result is that a fusion gene is created by juxtaposing the ABL1 gene on chromosome 9 (region q34) to a part of the BCR ( ... This gene is the ABL1 gene of chromosome 9 juxtaposed onto the breakpoint cluster region BCR gene of chromosome 22, coding for ... It arises from the translocation, which is termed t(9;22)(q34.1;q11.2), between chromosome 9 and chromosome 22, with breaks ...
The NLRP1 protein interacts strongly with caspase 2 and weakly with caspase 9. Overexpression of this gene was demonstrated to ... Ced-family members contain a caspase recruitment domain (CARD) and are known to be key mediators of programmed cell death. The ... NLRP1 has been shown to interact with caspase 9 and APAF1. GRCh38: Ensembl release 89: ENSG00000091592 - Ensembl, May 2017 ... Martinon F, Burns K, Tschopp J (2002). "The inflammasome: a molecular platform triggering activation of inflammatory caspases ...
In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. AIFM1 also ... "Mitochondrial release of caspase-2 and -9 during the apoptotic process". J. Exp. Med. 189 (2): 381-94. doi:10.1084/jem.189.2. ... a novel caspase-independent death effector released from mitochondria". Biochimie. 84 (2-3): 215-22. doi:10.1016/S0300-9084(02) ... "The C-terminal moiety of HIV-1 Vpr induces cell death via a caspase-independent mitochondrial pathway". Cell Death Differ. 9 ( ...
Pan G, O'Rourke K, Dixit VM (1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". J. Biol. Chem. 273 (10): 5841-5. ... The mouse counterpart of this protein is found to interact with Apaf1 and forms a protein complex with Caspase 9, which ... 8 (2): 83-9. doi:10.1007/s101470300015. PMID 12720100. Kang Y, Lee DC, Han J, et al. (2007). "NM23-H2 involves in negative ... 87 (9): 923-40. doi:10.1007/s00109-009-0495-7. PMID 19551325. BCL2L10 human gene location in the UCSC Genome Browser. BCL2L10 ...
Weng C, Li Y, Xu D, Shi Y, Tang H (Mar 2005). "Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related ... Pan G, O'Rourke K, Dixit VM (Mar 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". The Journal of Biological ... "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation". Proceedings of the National Academy of ... 12 (9): 1432-40. doi:10.1210/mend.12.9.0166. PMID 9731710. Ray R, Chen G, Vande Velde C, Cizeau J, Park JH, Reed JC, Gietz RD, ...
... to upregulate the activity of caspase-8. This causes cross talking of apoptotic signaling between caspase-8 and caspase-9 ... 100 (9): 3063-3067. doi:10.1182/blood-2002-03-0996. Schey, S.A. (15 August 2004). "Phase I Study of an Immunomodulatory ... 9 (11): 1625-30. doi:10.1016/s0960-894x(99)00250-4. PMID 10386948. Stewart, Scott G.; Spagnolo, Daniel; Polomska, Marta E.; Sin ... 66 (5): 323-9. doi:10.1016/j.biopha.2012.05.001. PMID 22770990. Prommer, E. E. (20 October 2009). "Review Article: Palliative ...
... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... Caspase-independent apoptosis. The characterization of the caspases allowed the development of caspase inhibitors, which ... Caspases Caspases play the central role in the transduction of ER apoptotic signals. Caspases are proteins that are highly ... There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ...
In at least some cases, the caspase activation is via a pathway that is dependent on caspase-9 but not on mitochondria. Some of ... Complex formation in the absence of ligand leads to caspase activation by a mechanism that is usually dependent on caspase ... specific caspases. Mutation of the caspase site(s) in the receptor, of which there is typically one or two, prevents the ... Thus these receptors may serve in caspase amplification, and in so doing create cellular states of dependence on their ...
... antagonizes both the precursor and mature forms of Smac and caspase-9". J. Biol. Chem. 280 (1): 174-82. doi:10.1074/jbc. ... "Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function". Nat. Cell Biol. 6 (9): 849-60. doi: ... 6 (9): 791-806. doi:10.1101/gr.6.9.791. PMID 8889548. Nagase T, Ishikawa K, Kikuno R, Hirosawa M, Nomura N, Ohara O (2000). " ... 9 (3): 99-106. doi:10.1093/dnares/9.3.99. PMID 12168954. Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, ...
Bonfoco E, Li E, Kolbinger F, Cooper NR (August 2001). "Characterization of a novel proapoptotic caspase-2- and caspase-9- ... Proteomics-based identification of proapoptotic caspase adapter protein as a novel serum marker of non-small cell lung cancer ... 54 (9): 2368-80. doi:10.1007/s00125-011-2212-7. PMID 21688198. Flach H, Rosenbaum M, Duchniewicz M, Kim S, Zhang SL, Cahalan MD ... 99 (9): 6398-403. Bibcode:2002PNAS...99.6398V. doi:10.1073/pnas.082112699. PMC 122960 . PMID 11972030. ...
2002). "Caspase-8 and Apaf-1-independent Caspase-9 Activation in Sendai Virus-infected Cells". The Journal of Biological ... In addition, several other molecules, most notably caspase-3, have been reported to co-purify with the apoptosome and caspase-3 ... Another targeted molecule for cancer therapy involves the caspase family and their regulators. The inhibition of caspase ... this initiator caspase can then activate effector caspases and trigger a cascade of events leading to apoptosis. The term ...
"Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity". Experimental Cell Research ... 61 (8): 3443-9. PMID 11309306. Weinmann AS, Bartley SM, Zhang T, Zhang MQ, Farnham PJ (Oct 2001). "Use of chromatin ... doi:10.1016/S0896-6273(02)00861-9. PMID 12372286. Song H, Xia SL, Liao C, Li YL, Wang YF, Li TP, Zhao MJ (Feb 2004). "Genes ... doi:10.1016/S0896-6273(02)00861-9. PMID 12372286. Kara NZ, Toker L, Agam G, Anderson GW, Belmaker RH, Einat H (Sep 2013). " ...
The caspase-9 then cleaves the proteins of the mitochondrial membrane, causing it to break down and start a chain reaction of ... Hampton MB, Orrenius S (Sep 1997). "Dual regulation of caspase activity by hydrogen peroxide: implications for apoptosis". FEBS ... The apoptosomes bind to and activate caspase-9, another free-floating protein. ... which is necessary for subsequent recruitment of Fas-associated protein with death domain and caspase 8 as well as apoptosis ...
Kuida, K (1998). "Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell 94: 325-337. ... como se observa nos ratos knockout para a caspase-3 ou caspase-9, xa que causa o desenvolvemento de exencefalia no prosencéfalo ... Kroemer G, Martin SJ (2005). "Caspase-independent cell death". Nature Medicine 11 (7): 725-30. PMID 16015365. doi:10.1038/ ... Oppenheim, RW (2001). "Programmed cell death of developing mammalian neurons after genetic deletion of caspases". Journal of ...
Caspase 3. Pro-apoptotic:. BAX. BAK1/Bcl-2 homologous antagonist killer. Bcl-2-associated death promoter. Anti-apoptotic:. Bcl- ... Apoptosis & Caspase 3 - PMAP The Proteolysis Map-animation. *UMich Orientation of Proteins in Membranes families/superfamily-78 ... Caspase 9 can then go on to activate caspase 3 and caspase 7, which are responsible for destroying the cell from within. ... This release of cytochrome c in turn activates caspase 9, a cysteine protease. ...
... of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase ... 278 (9): 7374-80. doi:10.1074/jbc.M209499200. PMID 12471034.. *^ Lee SF, Shah S, Li H, Yu C, Han W, Yu G (November 2002). " ... 277 (47): 45013-9. doi:10.1074/jbc.M208164200. PMID 12297508.. *^ Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, ... 274 (43): 30764-9. doi:10.1074/jbc.274.43.30764. PMID 10521466.. *^ Tesco G, Kim TW, Diehlmann A, Beyreuther K, Tanzi RE ( ...
Ab12490 Caspase 3 siRNA vector ?ab12496 Caspase 8 siRNA vector ?ab12504 Caspase 9 siRNA vector ... I have now added the western blot image for the caspase 3 knockdown. It can be viewed on www.abcam.com/ab12490. If you do have ... Im interesting in your siRNA vectars against several caspases but there are no datas on your web pages. Could you show me the ... between the sense portion of the siRNA sequence and the mRNA enables the nuclease enzyme to bind and cleave the caspase ...
Caspase 9 is responsible for initiating the caspase activation cascade during apoptosis. Apoptosis is a physiological mechanism ... of homeostasis and development, and caspases are the ex ... EC 3.4.22.-/Caspase 9 From MEDLINE®/PubMed®, a database of the ... Caspase 9 / metabolism*. Epidermis / enzymology*, pathology. Female. Humans. Immunohistochemistry / methods. Male. Middle Aged ... Counts of caspase 9 positive cells from the epidermis of psoriatic skin lesions were significantly lower than those seen in ...
Anti-Caspase-9 antibody (ab52298) has been cited in 22 publications. References for Human, Mouse, Rat in ICC/IF, IHC, IHC-Fr, ...
Rabbit polyclonal Caspase-9 p35 antibody. Validated in WB, IHC, Flow Cyt and tested in Rat, Human. Immunogen corresponding to ... Cleavages at Asp-315 by granzyme B and at Asp-330 by caspase-3 generate the two active subunits. Caspase-8 and -10 can also be ... Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to ... Anti-Caspase-9 p35 antibody (ab210611) at 1/300 dilution + Raji lysate. Secondary. Goat Anti-Rabbit IgG Antibody (H+L), HRP at ...
Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK.. Allan LA1, Morrice N, Brady S, Magee G, Pathak S, ... an initiator protease that activates caspase-3 and downstream caspases to initiate cellular destruction. However, survival ... Here, we show that the ERK MAPK pathway inhibits caspase-9 activity by direct phosphorylation. In mammalian cell extracts, ... We suggest that phosphorylation and inhibition of caspase-9 by ERK promotes cell survival during development and tissue ...
... derived caspase substrates are widely used for the colorimetric detection of various caspase activities. Cleavage of pNA ... pNA has maximum absorption around 408 nm.; Caspase-9 substrate; Ac-LEHD-pNA; Ac-Leu-Glu-His-Asp-pNA ... peptides by caspases generates pNA that is monitored colorimetrically at ~405 nm. ... pNA (4-nitroaniline)-derived caspase substrates are widely used for the colorimetric detection of various caspase activities. ...
Rabbit polyclonal pro Caspase-9 (phospho T125) antibody. Validated in WB, IHC and tested in Human. Cited in 9 publication(s). ... Cleavages at Asp-315 by granzyme B and at Asp-330 by caspase-3 generate the two active subunits. Caspase-8 and -10 can also be ... Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to ... Anti-pro Caspase-9 (phospho T125) antibody (ab138412) at 1/500 dilution + HeLa cells treated with TNF at 20 ng/ml for 5 minutes ...
Rabbit polyclonal Caspase-9 (phospho S196) antibody validated for WB, ELISA and tested in Human. Referenced in 1 publication. ... Cleavages at Asp-315 by granzyme B and at Asp-330 by caspase-3 generate the two active subunits. Caspase-8 and -10 can also be ... Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to ... References for Anti-Caspase-9 (phospho S196) antibody (ab61789). This product has been referenced in: *Dar AA et al. miRNA-205 ...
The human caspase-3, caspase-4, wild type, and mutant (C287S) caspase-9 cDNAs were cloned into the BamHI and XhoI sites of a ... including caspase-4, caspase-8, caspase-9, and nematode CED-3 in mammalian cells. The interaction with caspase-9 was mediated ... the relevance of the interaction between Apaf-1 and caspase-4 or caspase-8 is unclear. In contrast to caspase-9, Apaf-1 did not ... Lower) The expression of caspase-3 and -4 (B), caspase-9 (C), and CED-3 and Apaf-1 proteins (D). Reduced level of pro-caspase-9 ...
Within caspase-9s active site, in order for catalytic activity to occur there has to be specific amino acids in the right ... Caspase 8, NLRP1, and XIAP. The Proteolysis Map Caspase Caspase-3 Apoptosome Apaf-1 GRCh38: Ensembl release 89: ENSG00000132906 ... Similar to other caspases, caspase-9 has three domains: N-terminal pro-domain, large subunit, and a small subunit. The N- ... The introduction of caspases may also have medical benefits. In the context of graft versus host disease, caspase-9 can be ...
Human Caspase 9, Synthetic Peptide, Invitrogen 50µg Life Sciences:Protein Biology:Proteins:Peptides:Catalog Peptides ... 1 leads to activation of the protease which then cleaves and activates caspase-3. Caspase 9 promotes DNA damage-induced ... In humans, dysfunctional Caspase 9 expression vary from tissue to tissue. Low levels of Caspase 9 may play a role in cancer ... Caspase 9 is active as a heterotetramer, is present in the cytosol and, upon activation, translocates to the mitochondria. ...
What is caspase 9? Meaning of caspase 9 medical term. What does caspase 9 mean? ... Looking for online definition of caspase 9 in the Medical Dictionary? caspase 9 explanation free. ... The influence of compounds 2-4 on caspase 3/7, caspase 8 and caspase 9 activity in CCRF-CEM leukemia cells was detected using ... The influence of compound 3 on caspase 3/7, caspase 8 and caspase 9 activity in CCRF-CEM leukemia cells was detected using ...
Mouse monoclonal Caspase-9 antibody [10-1-87] validated for WB and tested in Human. Immunogen corresponding to recombinant full ... Cleavages at Asp-315 by granzyme B and at Asp-330 by caspase-3 generate the two active subunits. Caspase-8 and -10 can also be ... Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to ... All lanes : Anti-Caspase-9 antibody [10-1-87] (ab115792) at 1 µg/ml. Lane 1 : Jurkat cell lysate. Lane 2 : Jurkat cell lysate, ...
Rabbit Polyclonal Anti-Caspase-9 Antibody cited in 15 publications. Validated: WB, Flow-IC, IHC, IHC-Fr, IHC-P, IP. Tested ... Initiator caspases (such as Caspase-9) sense and respond to various signals i... Read full blog post.. ... Caspase 3, the executioner of apoptosis. Caspase-3 enzyme is a member of the family of endoproteases which regulate ... Caspase-3 is known as an executioner caspase in apoptosis because of its role in coordinating the destruction of cellular stru ...
Phospho-Caspase 9 (Thr125) Polyclonal Antibody from Invitrogen for Western Blot and Immunohistochemistry (Paraffin) ... 1 leads to activation of the protease which then cleaves and activates caspase-3. Caspase 9 promotes DNA damage-induced ... In humans, dysfunctional Caspase 9 expression vary from tissue to tissue. Low levels of Caspase 9 may play a role in cancer ... Cite Phospho-Caspase 9 (Thr125) Polyclonal Antibody. The following antibody was used in this experiment: Phospho-Caspase 9 ( ...
Order monoclonal and polyclonal Caspase 9 antibodies for many applications. Selected quality suppliers for anti-Caspase 9 ... caspase-8 (show CASP8 Antibodies) and caspase-9 contribute to the cyclic stretch-induced apoptosis, but functioned differently ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... anti-Caspase 8, Apoptosis-Related Cysteine Peptidase Antibodies * anti-Caspase 7, Apoptosis-Related Cysteine Peptidase ...
CASPALLO: Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene (CASPALLO). The safety and scientific validity ... CASPALLO: A Phase I Study Evaluating the Use of Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene After ... Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety ... iCaspase 9 Suicide Gene System. Methods Mol Biol. 2015;1317:87-105. doi: 10.1007/978-1-4939-2727-2_6. ...
BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell Damage and Repair, Diabetes, Obesity and Metabolic Syndrome, Stem Cell Biology, Gene Regulation, Signal Transduction, etc. BioVisions products are currently being sold in more than 60 countries worldwide.
... but possibly not the executioners caspase-3 and caspase-7, are required for primitive erythropoiesis in the early embryo. These ... Caspase-9 has a nonapoptotic function in Xenopus embryonic primitive blood formation.. [Hong Thi Tran, Mathias Fransen, ... Caspases constitute a family of cysteine proteases centrally involved in programmed cell death, which is an integral part of ... However, it has become clear that specific caspases also have functions independent of cell death. In order to identify novel ...
Apaf-3 was identified as a member of the caspase family, caspase-9. Caspase-9 and Apaf-1 bind to each other via their ... Activated caspase-9 in turn cleaves and activates caspase-3. Depletion of caspase-9 from S-100 extracts diminished caspase-3 ... Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade.. Li P1, Nijhawan ... We report here the purification of the third protein factor, Apaf-3, that participates in caspase-3 activation in vitro. ...
... triggered by the cell death receptor family and their ligands which signal through downstream adaptor molecules and the caspase ... Western Blot: Caspase 9 Antibody Cowan et al employed the Caspase 9 antibody to classify in vivo activation of caspases 9 and 3 ... Activated caspase 9 primary signaling occurs through caspase 3, which it cleaves and activates. The Caspase 9 antibody was used ... Among the subclass of initiator caspases that include subtypes -2, -8 and -9, caspase 9 is expressed in a variety of human ...
Compare and order Caspase 9 ELISA Kits. View citations, images, detection ranges, sensitivity, prices and more. Recommended ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... This protein is processed by caspase APAF1\; this step is thought to be one of the earliest in the caspase activation cascade. ... Search Caspase 9 ELISA Kits for other reactivities: Guinea Pig,. Pig (Porcine),. Cow (Bovine),. Goat,. Dog (Canine),. Chicken, ...
Anti-Caspase-9 antibody [E23] - BSA and Azide free (ab219590) has been cited in 23 publications. References for Human, Mouse, ... Yu E et al. Structural Determinants of Caspase-9 Inhibition by the Vaccinia Virus Protein, F1L. J Biol Chem 286:30748-58 (2011 ... Singh S et al. CXCR4-gp120-IIIB interactions induce caspase-mediated apoptosis of prostate cancer cells and inhibit tumor ... Lu H et al. The study of the Oxytropis kansuensis-induced apoptotic pathway in the cerebrum of SD rats. BMC Vet Res 9:217 (2013 ...
Caspase-9 Substrate LEHD-pNA. Provided in the ready-to-use form ...
... and the endogenous caspase inhibitor X-chromosome-linked inhibitor of apoptosis protein (XIAP) against recombinant caspase-9 ... Inhibitor specificity of recombinant and endogenous caspase-9. Ciara A. RYAN, Henning R. STENNICKE, Victor E. NAVA, Jennifer B. ... Inhibitor specificity of recombinant and endogenous caspase-9. Ciara A. RYAN, Henning R. STENNICKE, Victor E. NAVA, Jennifer B. ... Inhibitor specificity of recombinant and endogenous caspase-9 Message Subject (Your Name) has forwarded a page to you from ...
- Akt acts as an allosteric inhibitor of caspase-9 because the site of phosphorylation of serine-196 is far from the catalytic site. (wikipedia.org)
- The inhibitor affects the dimerization of caspase-9 and causes a conformational change that affects the substrate-binding cleft of caspase-9. (wikipedia.org)
- Isoform 2 lacks activity is an dominant-negative inhibitor of caspase-9. (abcam.com)
- The inhibitory potency of acetyl-Asp-Glu-Val-Asp-aldehyde ('Ac-DEVD-CHO'), benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone ('Z-VAD-FMK') and the endogenous caspase inhibitor X-chromosome-linked inhibitor of apoptosis protein ('XIAP') against recombinant caspase-9 were predictive of the efficacy of these compounds in a cell-free system. (biochemj.org)
- These results consolidate previous findings that CrmA is a potent inhibitor of caspase-9 in vitro , yet fails to block caspase-9-mediated cell death. (biochemj.org)
- At high FasL concentration (500 ng/mL), cell death was significantly, but not completely, inhibited by zVAD-fmk, a broad-spectrum caspase inhibitor, indicating that FasL can activate both caspase-dependent and -independent cell death signaling pathways. (mdpi.com)
- Caspase-3 inhibitor (Z-DEVD-FMK ) is a cell-permeable, potent, and irreversible inhibitor of caspase-3, caspase-6, caspase-7, caspase-8 and caspase-10. (scbt.com)
- See how others have used Caspase-3 Inhibitor. (scbt.com)
- The broad spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone failed to block the depolarization of mitochondrial membranes induced by resveratrol, further indicating that resveratrol action was independent of upstream caspase-8 activation via receptor ligation. (aacrjournals.org)
- In these experiments, the caspase activation pathways during receptor and chemical-mediated apoptosis were investigated using the broad spectrum caspase inhibitor Z-VAD-FMK. (aacrjournals.org)
- Therefore, in the present study, a siRNA targeting p38 MAPK (siRNA-p38 MAPK) and the caspase‑9 specific inhibitor z-LEHD-fmk were used to examine the crosstalk between p38 MAPK and caspase-9 during mitochondria-mediated apoptosis in the TαPcZn-PDT‑treated LoVo cells. (spandidos-publications.com)
- The Caspase-9 Inhibitor III, also referenced under CAS 403848-57-7, controls the biological activity of Caspase-9. (merckmillipore.com)
- A potent, irreversible inhibitor of caspase-9. (merckmillipore.com)
- Once inside the cell, the inhibitor binds covalently to the active caspase (10). (celltechnology.com)
- Cells were seeded in RPMI 1640 medium + 10% FBS with pretreatment with NAC, inhibitors of caspase-9 and -3 or a pan-caspase inhibitor, and then were exposed to 100 μM of emodin for 24 h. (nih.gov)
- In order to evaluate the roles of caspase-mediated pathways in emodin-induced apoptotic death of WEHI-3 cells, cells were pretreated with a pan-caspase inhibitor (Z-VAD-FMK), and then exposed to emodin. (nih.gov)
- MIHA is an inhibitor of apoptosis protein (IAP) that can inhibit cell death by direct interaction with caspases, the effector proteases of apoptosis. (rupress.org)
- Z-LEHD-FMK Irreversible Caspase-9 inhibitor. (apexbt.com)
- The caspase 9 inhibitor Z-LEHD-FMK protects human liver cells while permitting death of cancer cells exposed to tumor necrosis factor-related apoptosis-inducing ligand. (apexbt.com)
- Neuroprotection and functional recovery after application of the caspase-9 inhibitor z-LEHD-fmk in a rat model of traumatic spinal cord injury. (apexbt.com)
- Z-LEHD-FMK is a specific and irreversible inhibitor of caspase-9 . (apexbt.com)
- Abcam's Caspase 9 Inhibitor Drug Detection Kit provides an effective means for screening caspase inhibitors using fluorometric methods. (abcam.cn)
- Caspase activity (RFU) in presence of 0µM - 40µM of z-VAD-FMK (generic caspase inhibitor), assessed using LEHD-AFC as caspase 9 substrate and following Caspase 9 Inhibitor Drug Detection Kit ( ab102493 ) protocol. (abcam.cn)
- Caspase 3 is a cytoplasmic caspase with two isoforms (one acts as a dominant negative inhibitor), and is involved in the activation cascade for apoptosis execution. (novusbio.com)
- Thus, ARC represents an inhibitor of apoptosis expressed in muscle that appears to selectively target caspases. (pnas.org)
- Moreover, we show that, in contrast to the human enzymes, mouse caspase-7 is as efficient as caspase-3 at cleaving and thus inactivating ICAD (inhibitor of caspase-activated DNase), the inhibitor of apoptotic DNA fragmentation. (jneurosci.org)
- Caspase substrate specificity has been widely used in caspase based inhibitor and drug design. (wikipedia.org)
- Per usual in non-apoptotic growing cells caspase activated dnase is held in check inactivated in the cytoplasm thanks to the association with its inhibitor, inhibitor of caspase-activated DNase (ICAD) also known as DNA fragmentation factor 45 kDa (DFF45). (wikipedia.org)
- Biochemically, caspase-8 was found to enter the complex of the inhibitor of NF-κB kinase (IKK) with the upstream Bcl10-MALT1 (mucosa-associated lymphatic tissue) adapter complex which were crucial for the induction of nuclear translocation of NF-κB. (wikipedia.org)
- This protein binds inhibitor of apoptosis proteins (IAPs), thus freeing caspases to activate apoptosis. (wikipedia.org)
- Caspase activity and apoptosis inhibitor 1 is a protein that in humans is encoded by the CAAP1 gene. (wikipedia.org)
- Granzyme M is a regulatory protease that inactivates proteinase inhibitor 9, an endogenous inhibitor of granzyme B". J. Biol. (wikipedia.org)
- Granzyme B also cleaves the protein Bid, which recruits the proteins Bax and Bak to change the membrane permeability of the mitochondria, causing the release of cytochrome c (which is one of the parts needed to activate caspase-9 via the apoptosome), Smac/Diablo and Omi/HtrA2 (which suppress the inhibitor of apoptosis proteins (IAPs)), among other proteins. (wikipedia.org)
- Moreover, HtrA2/Omi is released in the cytosol from the mitochondria during apoptosis and uses its four most N-terminal amino acids to mimic a caspase and be recruited by inhibitor of apoptosis protein (IAP) caspase inhibitors such as XIAP and CIAP1/2. (wikipedia.org)
- Further neurological studies with Caspase 9 antibody in the autosomal dominant progressive disorder Huntington's disease (HD) helped define caspases 2, 6, and 7 downstream pathways as those responsible for selective neuronal death 4 . (novusbio.com)
- Therefore it remains important to gain a detailed understanding of the mechanisms behind native caspase-9 regulatory pathways and harness these mechanisms for therapeutic purposes. (umass.edu)
- Induction of stress signalling pathways JNK/SAPK causes release of cytochrome c from mitochondria and activation of apaf-1 (apoptosome), which in turn cleaves the pro-enzyme of caspase-9 into the active form. (creativebiomart.net)
- Historically, the regulation of the alternative splicing of caspase 9 by signaling pathways began with the lipid second messenger, ceramide. (aacrjournals.org)
- Our results from Western blotting suggest that emodin triggered apoptosis of WEHI-3 cells through the endoplasmic reticulum (ER) stress, caspase cascade-dependent and -independent mitochondrial pathways. (nih.gov)
- These data suggest that emodin triggered apoptosis of WEHI-3 cells through the ROS and caspase-dependent pathways. (nih.gov)
- Third, pathways upstream of caspase activation might be disrupted in tumor cells. (mdpi.com)
- This diversity is in part attributable to the fact that a major theme in L. majuscula biochemistry relies on the production of metabolites via polyketide synthases and nonribosomal peptide synthetases within specialized biosynthetic pathways ( 9 ). (pnas.org)
- Based on their structure and order in cell death pathways, caspases can be divided into initiator and effector caspases. (rupress.org)
- Besides these canonical apoptotic pathways there are also caspase independent pathways, triggered e.g. by granzyme B and A. These caspase independent pathways are thought to have evolved in response to viruses that inhibit caspases. (antibodies-online.com)
- Caspase-3 is activated in the apoptotic cell both by extrinsic (death ligand) and intrinsic (mitochondrial) pathways. (wikipedia.org)
- Moreover, the biochemical form of caspase-8 differed in the two pathways. (wikipedia.org)
- Caspase recruitment domain (CARD)-containing proteins, such as CARD8, are involved in pathways leading to activation of caspases or nuclear factor kappa-B (NF-κB) in the context of apoptosis or inflammation, respectively. (wikipedia.org)
- The PYD and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the inflammatory and apoptotic signaling pathways via the activation of caspase. (wikipedia.org)
- Both pathways induce cell death by activating caspases, which are proteases, or enzymes that degrade proteins. (wikipedia.org)
- The two pathways both activate initiator caspases, which then activate executioner caspases, which then kill the cell by degrading proteins indiscriminately. (wikipedia.org)
- The caspases can be activated through either the intrinsic (mitochondrial mediated) or extrinsic (death receptor mediated) apoptotic pathways. (wikipedia.org)
- In summary, HTRA2/Omi contributes to apoptosis through both caspase-dependent and -independent pathways. (wikipedia.org)
- The specimens were labelled immunohistochemically for binding of an anti-caspase 9 primary antibody. (biomedsearch.com)
- This peptide corresponds to 16 amino acids near the center of human Caspase-9.PEP-0029 can be used as a blocking peptide with polyclonal antibody PA5-19903. (fishersci.com)
- Immunohistochemistry-Paraffin: Caspase-9 Antibody [NB100-- Analysis Human Brain sections stained for cleaved Caspase-9 expression using this antibody at 1:2000. (novusbio.com)
- Immunohistochemistry-Paraffin: Caspase-9 Antibody [NB100-- Analysis of Capase-9 in mouse transplanted lung tumor section using anti-Caspase-9 antibody. (novusbio.com)
- This antibody detects both the pro- and active-Caspase 9 forms. (novusbio.com)
- The following antibody was used in this experiment: Phospho-Caspase 9 (Thr125) Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-36710, RRID AB_2553673. (thermofisher.com)
- The Caspase 9 antibody was used by Krajewski's group to characterize caspase 9 mitochondrial release during cytochrome c-dependent apoptosis and ischemia in their neuronal cell culture models 1 . (novusbio.com)
- Immunoblot studies with the Caspase 9 antibody allowed NIH researchers to dissect the complex signaling machinery downstream of cytochrome C, specifically that involving caspase 9 and Bax 2 . (novusbio.com)
- Cowan et al employed the Caspase 9 antibody to classify in vivo activation of caspases 9 and 3 in olfactory receptor neurons (ORNs) and found that caspase 3 is required for normal bulb development as well as mature differentiation through targeted apoptosis 3 . (novusbio.com)
- Herold's group used their characterization studies with Caspase 9 antibody to validate their preserved rat inguinal fat flap system as a permanent extracorporeal perfusion bioreactor system for examining fat cell death 5 . (novusbio.com)
- Immunohistochemistry analysis of paraffin-embedded human lung carcinoma tissue, using Caspase 9 (Cleaved-Asp353) Antibody. (genetex.com)
- Western blot analysis of extracts from NIH-3T3 cells, treated with Etoposide 25uM 60', using Caspase 9 (Cleaved-Asp353) Antibody. (genetex.com)
- WB analysis of HeLa cells treated with Etoposide 25uM (60mins) lysate using GTX86928 Caspase 9 (cleaved Asp330) antibody. (genetex.com)
- IHC-P analysis of human lung carcinoma tissue using GTX86928 Caspase 9 (cleaved Asp330) antibody. (genetex.com)
- There are currently no references for Caspase 9 (cleaved Asp330) antibody (GTX86928) . (genetex.com)
- Caspase 9 antibody LS-C148251 is an unconjugated rabbit polyclonal antibody to human Caspase 9 (CASP9) (aa188-206). (lsbio.com)
- Caspase 9 antibody LS-C12593 is an unconjugated mouse monoclonal antibody to human Caspase 9 (CASP9). (lsbio.com)
- Rabbit anti caspase-9 p10 antibody recognizes caspase-9, a member of the cysteine-aspartic acid protease family. (bio-rad-antibodies.com)
- The antibody will therefore detect pro-caspase-9 (as the motif is present) and the p10 caspase-9 fragment. (bio-rad-antibodies.com)
- The anti-active caspase-9 antibody recognizes only the cleaved caspase-9 (37 kDa). (antibody-antibodies.com)
- The affinity purified antibody recognizing the active forms of caspase-9 provides a new tool for identifying apoptotic cell populations in both tissue sections and cultured cells. (antibody-antibodies.com)
- The microtiter plate has been pre-coated with a monoclonal antibody specific for caspase-9. (biobool.com)
- Standards or samples are then added to the microtiter plate wells and caspase-9 if present, will bind to the antibody pre-coated wells, hi order to quantitatively determine the amount of caspase-9 present in the sample, a standardized preparation of horseradish peroxidase (HRP) -conjugated polyclonal antibody, specific for caspase-9 are added to each well to "sandwich" the caspase-9 immobilized on the plate. (biobool.com)
- Only those wells that contain caspase-9 and enzyme-conjugated antibody will exhibit a change in color. (biobool.com)
- Rabbit Anti-Phospho-Caspase-9 (Tyr153) Polyclonal Antibody, PE-Cy5 Conjugated antibody storage GENTAUR recommends for long therm storage to freeze at -24 C. For short time storage up to 30 days we suggest fridge storage at 1 to 10 C. Prevent multiple freeze taw cycles of Rabbit Anti-Phospho-Caspase-9 (Tyr153) Polyclonal Antibody, PE-Cy5 Conjugated. (antibody-antibodies.com)
- Rabbit Anti-Phospho-Caspase-9 (Tyr153) Polyclonal Antibody, PE-Cy5 Conjugated storing antibdies for longer storage periods of the Rabbit Anti-Phospho-Caspase-9 (Tyr153) Polyclonal Antibody, PE-Cy5 Conjugated we recommend - 21C or lower and for short periods lees than 1 month we suggest +5C fridge temperatures. (antibody-antibodies.com)
- Phospho-Caspase 9-S196 Antibody Peptide Affinity Purified Rabbit Polyclonal Antibody (Pab) Applications WB, IHC, E antibody storage Gentaur recommends for long therm storage to freeze at -24 C. For short time storage up to 30 days we suggest fridge storage at 1 to 10 C. Prevent multiple freeze taw cycles of Phospho-Caspase 9-S196 Antibody Peptide Affinity Purified Rabbit Polyclonal Antibody (Pab) Applications WB, IHC, E. (antibody-antibodies.com)
- Phospho-Caspase 9-S196 Antibody Peptide Affinity Purified Rabbit Polyclonal Antibody (Pab) Applications WB, IHC, E rabbit polyclonal These antibodies are very stable and can be stored up to 2 months at fridge temperature under 10C. (antibody-antibodies.com)
- Do not freeze taw, rather use Phospho-Caspase 9-S196 Antibody Peptide Affinity Purified Rabbit Polyclonal Antibody (Pab) Applications WB, IHC, E from the fridge if your use is less than 1 or 2 weeks. (antibody-antibodies.com)
- Rabbit Anti-Phospho-Caspase-9 (Tyr153) Polyclonal Antibody, Gold Conjugated ;Izotype IgG ;Reactivity Human , Mouse , Rat ;Application Electron Microscopy storing antibdies for longer storage periods of the Rabbit Anti-Phospho-Caspase-9 (Tyr153) Polyclonal Antibody, Gold Conjugated ;Izotype IgG ;Reactivity Human , Mouse , Rat ;Application Electron Microscopy we recommend - 21C or lower and for short periods lees than 1 month we suggest +5C fridge temperatures. (antibody-antibodies.com)
- GENTAUR suppliers human normal cells, cell lines, RNA extracts and lots of antibodies and ELISA kits to Human proteins as well as Rabbit Anti-Phospho-Caspase-9 (Tyr153) Polyclonal Antibody, Gold Conjugated ;Izotype IgG ;Reactivity Human , Mouse , Rat ;Application Electron Microscopy. (antibody-antibodies.com)
- Standards and test samples are added to the wells and along with a Caspase-9 detection antibody and the microplate is then incubated at room temperature. (abcam.cn)
- This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist antibody or TNF-related apoptosis inducing ligand in vivo. (wikipedia.org)
- Caspase-9 is an enzyme that in humans is encoded by the CASP9 gene. (wikipedia.org)
- On www.antibodies-online.com are 474 Caspase 9, Apoptosis-Related Cysteine Peptidase (CASP9) Antibodies from 35 different suppliers available. (antibodies-online.com)
- The observed casp9 activity in the ventral blood island (VBI) turns out to be independent of the activity of the downstream effectors casp3 and caspase-7 (casp7). (biologists.org)
- LS-F1857 is a 96-well enzyme-linked immunosorbent assay (ELISA) for the Qualitative detection of Human CASP9 / Caspase 9 in samples of Adherent Cell Cultures. (lsbio.com)
- Caspase 9 (also termed ICE-LAP6, Mch6, Apaf-3) is a member of cysteine protease family of caspases and is encoded by the CASP9 gene in humans. (novusbio.com)
- The objective of this study was to investigate whether polymorphisms of caspase-9 (CASP9) gene and RUNX3 are associated with IBD susceptibility and clinical phenotypes. (ox.ac.uk)
- Active caspase-9 works as an initiating caspase by cleaving, thus activating downstream executioner caspases, initiating apoptosis. (wikipedia.org)
- D609 stimulated FasL-induced cell death in caspase-8-deficient Jurkat cells, indicating that D609 acts downstream of caspase-8. (mdpi.com)
- In particular, we observed a time- and dose-dependent increase in the activities of the upstream caspase-9 and caspase-8 and of the downstream caspase-3. (oup.com)
- We aimed to clarify whether activation of caspases and Fas signalling are crucial for the onset of apoptosis after specific inhibition of TS and whether p53 plays a role in activation of these downstream processes. (elsevier.com)
- Downstream of caspase 8, the apoptotic signaling cascade bifurcates into a mitochondria-independent caspase 8/caspase 3 arm and a mitochondria-dependent, caspase 8/Bid/Bax/Bak/cytochrome c arm. (elsevier.com)
- Upon formation of the death-inducing signaling complex or the apoptosome, pro-caspase-8 or -9, respectively, are autoproteolytically processed, resulting in the activation of downstream caspases. (rupress.org)
- These results suggested that Tpl2 directly involved in apoptotic signal at the level of caspase-3 activation downstream of caspase-9, and that Tpl2 contributed to the exaggerated of ischemic liver injury through induction of apoptosis. (ajbm.net)
- Production of IL-1β downstream of caspase-11 requires another canonical inflammasome, called the NLRP3 inflammasome, that activates caspase-1. (wikipedia.org)
- 2006). Chronic oxidative stress also inhibits the downstream propagation of caspase-mediated apoptotic signals, which is the second hit in the 2-hit hypothesis of AD (Hampton et al. (wikipedia.org)
- A family of cysteine proteases (designated caspases) related to the C. elegans CED-3 appears to represent the effector arm of the apoptotic program ( 13 ). (pnas.org)
- Caspases are cysteine proteases, expressed as inactive precursors, that mediate apoptosis by proteolysis of specific substrates. (fishersci.com)
- Caspases constitute a family of cysteine proteases centrally involved in programmed cell death, which is an integral part of normal embryonic and fetal development. (sigmaaldrich.com)
- Caspase 7 (also known as CASP7, Mch3, ICE-LAP3, CMH-1) is a member of caspase family of cysteine proteases. (novusbio.com)
- At the core of the apoptotic process are caspases, a family of cysteine proteases. (antibodies-online.com)
- Apoptosis is a programmed form of cell death involving the degradation of cellular constituents by a group of cysteine proteases called caspases. (wikipedia.org)
- Metacaspases are members of the C14 class of cysteine proteases and thus related to caspases, orthocaspases and paracaspases. (wikipedia.org)
- Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK. (nih.gov)
- We suggest that phosphorylation and inhibition of caspase-9 by ERK promotes cell survival during development and tissue homeostasis. (nih.gov)
- Altogether, our data strongly indicate that the inhibition of ceramide conversion to complex sphingolipids by D609 is accompanied by an enhancement of FasL-induced caspase-dependent and -independent cell death in T lymphocytes. (mdpi.com)
- Based on known mechanisms, such as the unique inhibitory complex of caspase-9 and XIAP-BIR3, development of synthetic regulators can be envisioned, while other mechanisms such as zinc-mediated inhibition and CARD activation of caspse-9 remain undefined. (umass.edu)
- The activation of caspase-9 preceded that of caspase-8 and its specific inhibition completely prevented apoptosis. (oup.com)
- Inhibition of Caspase-9 restricted, while Apaf-1 promoted, Chlamydia pneumoniae infection in HEp-2, HeLa, and mouse epithelial fibroblast (MEF) cells. (nih.gov)
- interaction of rmEMMPRINex with U937 cells leads to inhibition of MCT1 membrane expression, intracellular activation of procaspase-9, followed by DNA fragmentation and apoptosis. (nih.gov)
- Inhibition of Mcl-1 and activation of caspases are critically involved in gallotannin-induced apoptosis in prostate cancer cells. (nih.gov)
- In conclusion, these results indicate that apoptosis induced after specific inhibition of TS is mediated via the caspases, but without clear involvement of Fas signalling. (elsevier.com)
- Note that in addition to apoptosis, Caspase-8 is also required for the inhibition of another form of programmed cell death called Necroptosis . (wikipedia.org)
- Inhibition of caspases can delay apoptosis, implicating a potential role in drug screening efforts. (abcam.cn)
- Consistent with the inhibition of caspase-8, ARC attenuated apoptosis induced by FADD and TRADD and that triggered by stimulation of death receptors coupled to caspase-8, including CD95/Fas, tumor necrosis factor-R1, and TRAMP/DR3. (pnas.org)
- Systemic treatment of zebrafish or local treatment of the chick chorioallantoic membrane with ScA resulted in dose-dependent inhibition of angiogenesis, whereas topical treatment blocked tumor growth among caspase-8-expressing tumors. (pnas.org)
- Cowpox is a orthopox virus that increases their chances of survival and infection by inhibition of specific caspases and preventing inflammatory responses and apoptosis. (wikipedia.org)
- Inhibition of caspase 8 also prevents cell death signals by ligation of a TNF super family member known as death receptors, that signal for apoptosis through caspase 8. (wikipedia.org)
- These findings suggest that caspases other than caspases 2 and 9 can promote cytochrome c release and initiate Bcl-2-regulated apoptosis. (edu.au)
- Aspirin and Curcumin (diferuloylmethane) too activate caspase-8 to cleave and translocated Bid, induced a conformational change in and translocation of Bax and cytochrome-c release. (wikipedia.org)
- 1997). Substrate specificities of caspase family proteases. (anaspec.com)
- Furthermore, an interaction was discovered between CARD and the catalytic core of caspase-9 in the presence of a properly formed substrate binding groove, a potential mechanism utilized by the apoptosome for activation of the enzyme. (umass.edu)
- Together these findings provide mechanistic insight into a new level of caspase-9 regulation, prompting speculation that the CARD may also play a role in the recruitment or recognition of substrate. (biochemj.org)
- Caspase enzymes specifically recognize a 4 amino acid sequence (on their substrate) which necessarily includes an aspartic acid residue. (celltechnology.com)
- 9. Add 5 μl of the 4 mM substrate LEHD-pNA (200 μM final conc. (antibody-antibodies.com)
- One unit is defined as the amount of enzyme that cleaves 1nmol of the caspase substrate LEHD-pNA per hour at 37°C in a reaction solution containing 50mM HEPES, pH 7.2, 50mM NaCl, 0.1% CHAPS, 10mM EDTA, 5% glycerol and 10mM DTT. (vwr.com)
- Active caspase 9 cleaves the synthetic substrate to release free AFC which can then be quantified by fluorometry. (abcam.cn)
- The ready-to-use caspase substrate provides an economic alternative for researchers who perform large amount of caspase assays. (antibody-antibodies.com)
- Caspase 3 and caspase 7 share similar substrate specificity by recognizing tetra-peptide motif Asp-x-x-Asp. (wikipedia.org)
- DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. (wikipedia.org)
- At this moment, no structural variants have been reported where the substrate specificity would change to an acidic residue (aspartic acid), like in true caspases. (wikipedia.org)
- Several reports have demonstrated that caspase-8, and its substrate BID, are frequently activated in response to certain apoptotic stimuli in a death receptor-independent manner. (wikipedia.org)
- Synthetic peptide within Human Caspase-9 p35 aa 20-69 conjugated to keyhole limpet haemocyanin. (abcam.com)
- Synthetic peptide corresponding to Human Caspase-9. (abcam.com)
- Synthesized phosphopeptide derived from human Caspase 9 around the phosphorylation site of serine 196 (F-S-SP-L-H). (abcam.com)
- The antiserum was produced against synthesized peptide derived from human Caspase 9. (genetex.com)
- The N-terminal fragment of human Caspase 9 (amino acid residues 1-134). (lsbio.com)
- Intended Use Human caspase 9 ELISA Kit allows for the in vitro quantitative determination of caspase 9 , concentrations in serum, Plasma , tissue homogenates and Cell culture supernates and Other biological fluids. (biobool.com)
- Inquiry About Human caspase 9 ELISA Kit If you hope to order it or contact us directly, please contact us via [email protected] (biobool.com)
- Structure of caspase-1 (CASP1), originally called interleukin-1 beta-converting enzyme (ICE), the first human caspase to be identified. (wikipedia.org)
- Abcam's Caspase-9 Human in vitro ELISA (Enzyme-Linked Immunosorbent Assay) kit is designed for accurate quantitative measurement of Human Caspase-9 concentrations in cell lysate, cell culture supernatant and serum. (abcam.cn)
- 2. Caspase antibodies are classical tools for detecting inactive (pro) and active (cleaved) forms of the enzymes. (novusbio.com)
- Caspase-9 specific antibodies have been precoated onto 96-well plates. (abcam.cn)
- We also demonstrate that S. aureus -induced cell death and caspase activation were mediated by α-toxin, a major cytotoxin of S. aureus , since both events were abrogated by two different anti-α-toxin antibodies and could not be induced with supernatants of an α-toxin-deficient S. aureus strain. (rupress.org)
- Each caspase contains conserved residues important for specific proteolytic activity cleaving after aspartic acid residues ( 13 ). (pnas.org)
- Caspases have the ability to cleave after aspartic acid residues. (abcam.cn)
- Each caspase contains conserved sequences important for proteolytic activity cleaving after specific aspartic acid residues ( 6 ). (pnas.org)
- This specificity allows caspases to be incredibly selective, with a 20,000-fold preference for aspartic acid over glutamic acid. (wikipedia.org)
- Under normal circumstances, caspases recognize tetra-peptide sequences on their substrates and hydrolyze peptide bonds after aspartic acid residues. (wikipedia.org)
- DFFA is encoded by an alternatively encrypted mRNAs originating two distinct forms: short (ICAD-S) and long (ICAD-L), which act like a specific chaperone ensuring the correct CAD's folding Besides, it contains two aspartic acid residues (Asp117 and Asp224) where CAD is identified and, consequently, it stays bounded until Caspase-3 splits this union. (wikipedia.org)
- The region of homology shared between Apaf-1 and the prodomains of CED-3-like proteases has been termed caspase recruitment domain ( 19 ). (pnas.org)
- Caspase-9 contains a Caspase Activation and Recruitment Domain (CARD), which enables caspase-9 to form a tight interaction with the apoptosome, a heptameric activating platform. (biochemj.org)
- The caspase-9 CARD has been thought to be principally involved in recruitment to the apoptosome, but its roles outside this interaction have yet to be uncovered. (biochemj.org)
- We have identified and characterized ARC, apoptosis repressor with caspase recruitment domain (CARD). (pnas.org)
- TNF receptor-1) that leads to the recruitment of the adapter molecule Fas-activated death domain (FADD) * and pro-caspase-8 into a death-inducing signaling complex. (rupress.org)
- Ced-family members contain a caspase recruitment domain (CARD) and are known to be key mediators of programmed cell death. (wikipedia.org)
- The oligomerization of Apaf-1 appears to be accompanied by synchronized recruitment of procaspase-9 to the CARD motif at the Apaf-1 N-terminus. (wikipedia.org)
- Tissue expression of caspase-9 is ubiquitous with the highest expression in the brain and heart, specifically at the developmental stage of an adult in the heart's muscle cells. (wikipedia.org)
- The caspase 9 positive cell fraction was calculated for both epidermal and dermal cells in psoriatic lesions and healthy control skin. (biomedsearch.com)
- Caspase-9 is phosphorylated at Thr 125, a conserved MAPK consensus site targeted by ERK2 in vitro, in a MEK-dependent manner in cells stimulated with epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA). (nih.gov)
- Here we show that a mammalian homolog of CED-4, Apaf-1, can associate with several death proteases, including caspase-4, caspase-8, caspase-9, and nematode CED-3 in mammalian cells. (pnas.org)
- Bcl-X L , an antiapoptotic member of the Bcl-2 family, was shown to physically interact with Apaf-1 and caspase-9 in mammalian cells. (pnas.org)
- Expression of Bcl-X L inhibited the association of Apaf-1 with caspase-9 in mammalian cells. (pnas.org)
- Significantly, recombinant Bcl-X L purified from Escherichia coli or insect cells inhibited Apaf-1-dependent processing of caspase-9. (pnas.org)
- The influence of compound 3 on caspase 3/7, caspase 8 and caspase 9 activity in CCRF-CEM leukemia cells was detected using Caspase-Glo 3/7, Caspase-Glo 8 and Caspase-Glo 9 Assay kits (Promega, Germany). (thefreedictionary.com)
- The influence of compounds 2-4 on caspase 3/7, caspase 8 and caspase 9 activity in CCRF-CEM leukemia cells was detected using Caspase-Glo 3/7, Caspase-Glo 8 and Caspase-Glo 9 Assay kits (Promega, Germany). (thefreedictionary.com)
- This study is a phase I dose finding trial to determine if chimeric antigen receptor T (CAR-T) cells targeting the CD19 antigen and containing the inducible caspase 9 safety switch can be safely administered to adult subjects with relapsed or refractory B-cell Lymphoma. (clinicaltrials.gov)
- Kim W-H, Song H-O, Choi H-J, Bang H-I, Choi D-Y, Park H. Ethyl Gallate Induces Apoptosis of HL-60 Cells by Promoting the Expression of Caspases-8, -9, -3, Apoptosis-Inducing Factor and Endonuclease G. International Journal of Molecular Sciences . (mdpi.com)
- Western Blot Analysis: 0.5-2 ug/ml detects the proform of Caspase 9 in RIPA lysates from both A431 and Raji cells. (lsbio.com)
- 0.5-2 ug/ml of a previous lot detected the proform and cleaved Caspase 9 in RIPA lysates from HFF cells. (lsbio.com)
- Jurkat cells were treated with 1 µM staurosporine to induce caspase 9 activity (top), or treated with a control (bottom). (neuromics.com)
- Almost all cells in the induced sample (top) fluoresce green therefore they have activated caspase 9. (neuromics.com)
- To further determine the biological importance of this mechanism, we employed RNA oligonucleotides to redirect caspase 9 pre-mRNA splicing in favor of caspase 9b expression, which resulted in an increase in the IC 50 of non-small cell lung cancer (NSCLC) cells to daunorubicin, cisplatinum, and paclitaxel. (aacrjournals.org)
- Transforming growth factor beta-dependent sequential activation of Smad, Bim, and caspase-9 mediates physiological apoptosis in gastric epithelial cells. (semanticscholar.org)
- Emodin stimulated the activities of caspase-3 and -9 of WEHI-3 cells. (nih.gov)
- Cells were determined the caspase-3, -8, and -9 activity (a) and percentage of viable cells (b) as described in Section 2. (nih.gov)
- Caspases are synthesized as inactive pro-enzymes that are processed to active form in cells undergoing apoptosis. (antibody-antibodies.com)
- Expression of mutant caspase-9 correlated with a downregulation of BAFFR (B-cell-activating factor belonging to the TNF family (BAFF) receptor) in B cells and ICOS (inducible T-cell costimulator) in T cells. (nih.gov)
- Levels of caspase-9, caspase-10, MAVS, and pIRF7 in mononuclear cells and the disease activity index (SLEDAI) in the systemic lupus erythematosus patients were determined. (nih.gov)
- caspase-9 mediates Puma activation to determine the threshold for overcoming chemoresistance in cancer cells. (nih.gov)
- Additionally, scientists have used caspases as cancer therapy to kill unwanted cells in tumours. (wikipedia.org)
- Further analysis showed that the enzymatic activity of caspase-8 was inhibited by ARC in 293T cells. (pnas.org)
- We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. (mdpi.com)
- First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. (mdpi.com)
- We thus propose a model wherein caspases are preserved in tumor cells due to their functional contributions to development and progression of tumors. (mdpi.com)
- Sensitivity to ScA was significantly increased among cells expressing caspase 8, whereas siRNA knockdown of caspase 8 increased survival after exposure to ScA. (pnas.org)
- Consistent with the induction of apoptosis via the lipid compartment, we noted accumulation and aggregation of ceramide in treated cells and subsequent colocalization with caspase 8. (pnas.org)
- We show that caspase activation and DNA fragmentation were induced not only when Jurkat T cells were infected with intact bacteria, but also after treatment with supernatants of various S. aureus strains. (rupress.org)
- Low levels of caspase-7 expression and activation correlate with lack of DNA fragmentation in 129- Casp3 -/- apoptotic precursor neurons, whereas B6- Casp3 -/- cells, which can fragment their DNA, show higher levels of caspase-7 expression and activation. (jneurosci.org)
- Analysis of adult mice reconstituted with caspase-2−/−9−/− hematopoietic cells revealed that the absence of both caspases did not influence hematopoietic development. (edu.au)
- However, these cells were exposed to oxidative stress in the presence of FeSO 4 or CuSO 4 and ascorbate, which caused the activation of caspase-3 and caspase-9, resulting in apoptosis of the cells. (mdpi.com)
- The zymogen feature of caspase-3 is necessary because if unregulated, caspase activity would kill cells indiscriminately. (wikipedia.org)
- Further work revealed that caspase-8 was essential for the induction of the transcription factor "nuclear factor κB" (NF-κB) after stimulation through antigen receptors, Fc receptors, or Toll-like receptor 4 in T, B, and natural killer cells. (wikipedia.org)
- The study used HepG2 human liver carcinoma cells to test this, and found that tumstatin upregulated the expression of Caspase-9, Fas, Bax, Bid, and p53 while downregulating Bcl-2. (wikipedia.org)
- Chromosome 9 spans about 138 million base pairs of nucleic acids (the building blocks of DNA) and represents between 4 and 4.5 percent of the total DNA in cells. (wikipedia.org)
- 8 and Caspase 9 colorimetric assay: R&D Systems, Inc. (thefreedictionary.com)
- Caspase-Glo 9 Assay System - Apoptosis Assays and Systems, Promega - Model FPPAG8210 - Each : Apo-ONE Homogeneous Caspase-3/7 Assay: Use for fast, sensitive, fluorescent measurement of caspase-3 and -7 activity in a homogenous format. (egeneralmedical.com)
- His laboratory developed an in-vitro assay for the activation of the apoptosis related proteinase Caspase-3. (wikipedia.org)
- Cleavages at Asp-315 by granzyme B and at Asp-330 by caspase-3 generate the two active subunits. (abcam.com)
- The presence of the large or small subunits in western blots is considered to be a marker of caspase activation. (novusbio.com)
- The caspases are synthesized as inactive precursors that are proteolytically processed to generate active subunits. (pnas.org)
- Caspases are synthesized as inactive proenzymes and proteolytically processed to form an active complex composed of two heterodimeric subunits of ∼10 and 20 kD. (rupress.org)
- Caspase-3, in particular, (also known as CPP32/Yama/apopain) is formed from a 32 kDa zymogen that is cleaved into 17 kDa and 12 kDa subunits. (wikipedia.org)
- Caspase-1, normally in its physiologically inactive zymogen form, autoactivates when it is assembled into the filamentous inflammasome complex by autoproteolysis into the p10 and p20 subunits. (wikipedia.org)
- Pro-caspase-2 contains two subunits, p19 and p12. (wikipedia.org)